The gastrointestinal (GI) tract is a continuous channel through the body that consists of the esophagus, the stomach, the small intestine, the large intestine, and the rectum. Its primary functions are to move the intake of food for digestion before storing and ultimately expulsion of feces from the rectum through the anal sphincter. The mechanical behavior of GI tissues thus plays a crucial role for GI function in health and disease. The mechanical properties are typically characterized by a constitutive biomechanical model, which is a mathematical representation of the relation between load and deformation in a tissue. Hence, validated biomechanical constitutive models are essential to characterize and simulate the mechanical behavior of the GI tract under physiological and pathological conditions. Numerous constitutive models have consequently been proposed over the past three decades, mainly inspired by work done in cardiovascular tissues. Here, a comprehensive review of these constitutive models is provided. This review is limited to studies where a model of the strain energy function is proposed to characterize the stress-strain relation of a GI tissue. Several needs are identified for more advanced modeling of GI biomechanics including: 1) Microstructural models that provide actual structure-function relations; 2) Validation of coupled electro-mechanical models accounting for active muscle contractions; 3) Human data under physiological and pathological conditions to develop and validate models. The findings from this review provide guidelines for using existing constitutive models as well as perspective and directions for future studies aimed at establishing new constitutive models for GI tissues.

Since coffee has been shown to influence positively the metabolism of subjects with metabolic syndrome (MetS), we aimed to evaluate the short- and long-term effects of a coffee-based supplement on different features of diet-induced MetS. 24 Sprague Dawley rats were divided into control or nutraceuticals groups to receive a high-fat/high fructose diet with or without a mixture of caffeic acid (30 mg/day), trigonelline (20 mg/day), and cafestol (1 mg/day) for 12 weeks. An additional 11 rats were assigned to an acute crossover study. In the chronic experiment, nutraceuticals did not alter body weight or glycemic control but improved fed hyperinsulinemia and HOMA-IR, and plasma adiponectin levels. The impact of nutraceuticals on post-prandial glycemia tended to be more pronounced after acute administration than at the end of the chronic study. Circulating and intrahepatocellular alanine transaminase activity, assessed by hyperpolarized-¹³C NMR spectroscopy, were reduced by coffee nutraceuticals at endpoint. There was also a tendency towards lower liver triglyceride content and histological steatosis score in the intervention group. In conclusion, a mixture of coffee nutraceuticals improved insulin sensitivity and exhibited hepatoprotective effects in a rat model of MetS. Higher dosages with or without caffeine deserve to be studied in the future.

Literature is inconsistent as to how coffee affects the features of the metabolic syndrome (MetS), and which bioactive compounds are responsible for its metabolic effects. We aimed to compare the in-vivo effects of unfiltered coffee with a selected mixture of its compounds on diet-induced MetS. 24 male Sprague-Dawley rats were fed a high-fat (35% W/W) food plus 20% W/W fructose in drinking water for 14 weeks, and were randomized into three groups: control, coffee, or nutraceuticals (5-O-caffeoylquinic acid, caffeic acid, and trigonelline). Coffee or nutraceuticals were provided in drinking water in a dosage equal to 4 cups/day in a human. Compared to the controls, only coffee supplementation decreased total food intake, weight gain, and estimated average plasma glucose. Surrogate measures of insulin resistance (fasting insulin, HOMA-IR, and oral glucose tolerance) were improved at endpoint in the coffee group. Circulating triglyceride levels were also reduced by coffee. Histopathological and quantitative measurements indicated lower grades of liver steatosis after long-term coffee consumption. In conclusion, a combination of phenolic acids and trigonelline was not as effective as coffee per se in improving the components of the MetS. This points to the role of other coffee chemicals and a potential synergism between compounds.

Aronia berries contain antioxidants that may have health promoting properties e.g., demonstrated positive effects on hypertension and dyslipidemia. There is a close link between cardiovascular diseases and hypertension and dyslipidemia, and cardiovascular events are the leading cause of death among subjects with T2D. Thus, we investigated the effect of 8 weeks supplementation with fermented aronia extract (FAE), non-fermented aronia extract (AE) and placebo on cardiovascular risk factors. The extracts were incorporated into snack bars containing 34 g (37%) aronia extract, or 17 g (21%) wheat bran for placebo, as well as raisins and coconut oil. The study was randomized and blinded with a triple-cross-over design. We examined the effects of aronia extracts on blood pressure, adiponectin and high-sensitive C-reactive protein and found no effects. After supplementation with placebo, there were significantly higher total-cholesterol, LDL-cholesterol, and HDL-cholesterol, with the placebo group showing significantly higher increases in total-cholesterol and LDL-cholesterol than the FAE group. Furthermore, we observed an increase in HDL-cholesterol in the AE group and an increase in triglyceride in the FAE group. Thus, we assume that raisins may have increased the participants’ cholesterol levels, however, with both AE and FAE having the potential to prevent this increase.

The functioning of forest ecosystems depends on the taxonomic and ecological diversity of soil fungi. Urbanization is increasing worldwide and is regarded a major driver of environmental change altering local species assemblages in urban forest. We investigated whether the degree of urbanization and local forest characteristics affect the soil fungal community in 20 beech forests located along a rural–urban gradient in the city of Basel and its suburbs (Switzerland). We analyzed their soil fungal communities by DNA metabarcoding of the rDNA ITS2 region and related these data to local forest vegetation characteristics and soil properties. The number of fungal OTUs in the 20 forests examined ranged from 170 to 303. Richness, diversity and evenness of fungal OTUs were all significantly affected by the degree of urbanization, but in different ways. OTU richness was highest in forests in areas with a low degree of urbanization and lowest in forests in rural areas. In contrast, the diversity of OTUs increased with increasing degree of urbanization. Different fungal phyla and fungal guilds showed distinct patterns in their relative abundance along the rural-urban gradient. The degree of urbanization reduced the relative abundance of symbiotrophic fungi, but increased that of saprotrophic and pathotrophic fungi. Our results show that urbanization alters soil fungal community, which in turn can lead to changes in forest ecosystems.

Estimating the infection risks in indoor environments comprises the assessment of the behavior of virus-laden aerosols, i.e. spreading, mixing, removal by air purifiers etc. A promising experimental approach is based on using non-hazardous surrogate aerosols of similar size, e.g. salt particles, to mimic the virus aerosol behavior. This manuscript addresses the issue how a successful transfer of such experiments can be accomplished. Corresponding experiments in two very different environments, a large community hall and a seminar room, with optional use of air purifiers in various constellations were conducted. While high particle concentrations are advantageous in terms of avoiding influence of background aerosol concentrations, it is shown that appropriate consideration of aggregation and settling are vital to theoretically describe the experimentally determined course of particle concentrations. A corresponding model equation for a well-mixed situation is derived and the required parameters are thoroughly determined in separate experiments independently. It is demonstrated that clean air delivery rates (CADR) of air purifiers determined with this approach may differ substantially from common approaches not explicitly taking into account aggregation.

Numerical simulations of standard situations in the transition region from gas kinetics to fluid dynamics at small Mach numbers indicate a clear dependence of the simulation results on the underlying kinetic model (here: nonlinear and linearized Boltzmann collision operator vs. BGK relaxation model). We develop an improved mathematical framework (trace theory) to explain these differences. In particular we reveal certain deficiencies for the classical BKG system as well as for the standard Navier Stokes approach.

The structures of recently discovered primarolides A and B suggest their non-enzymatic formation from a common 2-formylbenzophenone precursor. This hypothesis is based on the experimentally proven facile conversion of pestalone (also a 2-formyl-benzophenone) either into the isomeric lactone pestalalactone or the structurally related isoindolinone pestalachloride A. In a related fashion, the racemic isoindolinone natural product mariline A is supposed to biosynthetically originate from the corresponding keto-aldehyde and an aniline, as experimentally supported by model studies. Due to the close structural relationship with known systems, it appears highly probable that primarolides A and B were generated under the fermentation conditions from a massarinin-related 2-formylbenzophenone (proprimarolide) by reaction either with aniline or a nucleophilic catalyst, respectively. Suberoylanilide hydroxamic acid (SAHA), used as an additive during the fermentation, is supposed to act both as a source of aniline and as a nucleophilic catalyst.

TAU is the main disease driver in Alzheimer’s and many other sporadic and genetic tauopathies. TAU is differently spliced, the role of individual splice-isoforms unclear. Murine Mapt-KO mice are healthy, and protected from Alzheimer’s, but no such case has been reported in humans. Using gnomad database, we here demonstrate that the only isoform expressed during fetal human brain development is intolerant to mutation, while other brain and peripheral nervous system TAU isoforms are dispensable. With TAU targeted therapies for Alzheimer’s and other tauopathies on the rise, we caution that TAU is essential human brain development.

The concept of an economy that is circular and without the need for material or energy input has an irresistible appeal to those who have recognized that planetary boundaries exist and that resources are not unlimited. Thus, in the public discourse its narrative outperforms other lines of arguments when it comes to keeping radical critics of destructive extractivism and the growth imperative in check and averting the uptake of diverging opinions by larger segments of the population and government bodies. Moreover, the myth of a circular economy has the additional benefit that it can win over parts of the environmental movement that dread radical and transformative change, particularly in the urban milieus of a middle-class that enjoys the privileges of the current social order. In this paper I argue that the circular economy narrative tends to hinder the necessary systemic transformation while entailing a wide range of specific measures that deserve to be recognized for their merit.

With the Paris Agreement, countries are obliged to report greenhouse gas (GHG) emission reduc-tions, which will ensure that the global temperature increase is maintained well below 2C. The Parties will report their Nationally Determined Contributions in terms of plans and progress to-wards these targets during the postponed COP26 in Glasgow in November 2021. These commit-ments however do not take significant portions of the consumption related emissions related to countries imports in to account. Similarly, the majority of companies that report their emissions to CDP also do not account for their embodied value-chain related emissions. Municipalities, on the path towards carbon neutrality in accordance with the methods outlined by C40, also do not in-clude imported and embodied CO2e in their total emission tallies. So, who is responsible for these emissions - the producer or the consumer? How can we ensure that the NDC's, municipalities and companies reduction targets share the responsibility of the emissions in the value-chain thus en-suring that targets and plans become, sustainable, climate fair, and just in global value chains? Today the responsibility lays with the producer, which is not sustainable. We have the outline for the tools needed to quantify and transparently share the responsibility between producers and consumers at corporate, municipal and national level based on an improved understanding of the attendant sources, causes, flows and risks og GHG emissions globally. Hybrid LCA/EEIO models can for example be further developed. This will, in the end, enable everyday consumption to support a more sustainable, green and low carbon transition of our economy.

Abstract: Traffic collisions cause a huge problem of public health in low and middle income countries.. The safe system approach is generally considered as the leading concept on the way to road safety. Based on the fundamental premise that humans make mistakes, the overall traffic system should be ‘forgiving’. Sustainable safe road design is one of the key elements of the safe system approach. However, the road design principles behind the safe system approach are certainly not leading in today’s infrastructure developments in most LMICs. Cities are getting larger and road networks are expanding. In many cases, existing through-roads in local communities are up-graded, resulting in heavy traffic loads and high speeds on places, that are absolutely not suited for this kind of through-traffic. Furthermore a safe system would require that functional design properties of cars and roads would be conceptually integrated, which is not the case at all. Although advanced driver assistance systems are on their way of development for quite a long period, their potential role in the safe system concept is mostly unclear and at least strongly underexposed. The vision on future cars is dominated by the concept of automation. This paper argues that the way to self-driving cars, should take a route via the concept of guidance, i.e. vehicles that guide drivers, both on self-explaining roads and on more or less unsafe roads. Such an in-vehicle support system may help drivers to choose transport mode, route and speed, based on criteria related to safety and sustainability. It is suggested to develop a driver assistance system using relatively simple and cheap technologies, particularly for the purpose of use in LMICs. Such a GUIDE (Generic User Interface for Driving Evolution) may make roads self-explaining - not only by their physical design characteristics - but also by providing in-car guidance for drivers. In future the functional characteristics of both cars and roads should be conceptualized into one integrated safe system, in which the user plays the central role. As such GUIDE may serve as the conceptual bridge between vehicle and roadway characteristics. It is argued that GUIDE is necessary to bring a breakthrough in road safety developments in LMICs and also give an acceleration towards zero fatalities in HICs.

Quantum loops are processes that constitute quantum objects. In the causal model of quantum loops and quantum objects presented here, the nonlinear processes involve the elementary units of spacetime and the associated elementary units of quantum fields. As such, quantum loop processes are the sources of gravitational fields (i.e., spacetime curvature) and of the quantum objects wave function. The model may be viewed as a derivative of loop quantum gravity, spin networks and causal dynamical triangulation, although significant deviations to these theories exist. The causal model of quantum loops is based on a causal model of spacetime dynamics where space(-time) consists of interconnected space points, each of which is connected to a small number of neighboring space points. The curvature of spacetime is expressed by the density of these space points and by the arrangement of the connections between them. The quantum loop emerges in a nonlinear collective behavioral process from a collection of space points that carry energy and quantum field attributes.

Based on a local causal model of the dynamics of curved discrete spacetime, a causal model of quantum field theory in curved discrete spacetime is described. On the elementary level, space(-time) is assumed to consists of interconnected space points. Each space point is connected to a small discrete set of neighboring space points. Density distribution of the space points and the lengths of the space point connections depend on the distance from the gravitational sources. This leads to curved spacetime in accordance with general relativity. Dynamics of spacetime (i.e., the emergence of space and the propagation of space changes) dynamically assigns "in-connections" and "out-connections" to the affected space points. Emergence and propagation of quantum fields (including particles) are mapped to the emergence and propagation of space changes by utilizing identical paths of in/out-connections. Compatibility with standard quantum field theory (QFT) requests the adjustment of the QFT techniques (e.g., Feynman diagrams, Feynman rules, creation/annihilation operators), which typically apply to three in/out connections, to n > 3 in/out connections. In addition, QFT computation in position space has to be adapted to a curved discrete space-time.

Based on a local causal model of the dynamics of curved discrete spacetime, a causal model of quantum field theory in curved discrete spacetime is described. At the elementary level, space(-time) is assumed to consists of interconnected space points. Each space point is connected to a small discrete set of neighbor space points. Density distribution of the space points and the lengths of the space point connections depend on the distance from the gravitational sources. This leads to curved spacetime in accordance with general relativity. Dynamics of spacetime (i.e., the emergence of space and the propagation of space changes) dynamically assigns "in-connections" and "out-connections" to the affected space points. Emergence and propagation of quantum fields (including particles) are mapped to the emergence and propagation of space changes by utilizing identical paths of in/out-connections. Compatibility with standard quantum field theory (QFT) requests the adjustment of the QFT techniques (e.g., Feynman diagrams, Feynman rules, creation/annihilation operators), which typically apply to three in/out connections, to n > 3 in/out connections. In addition, QFT computation in position space has to be adapted to a curved discrete space-time.

Metal-catalyzed lipid oxidation is a major factor in food waste, as it reduces shelf life. Addressing this issue, our study investigates the potential of hydrolysates derived from potato protein, a by-product of potato starch production, as metal chelating antioxidants. Through sequential enzymatic hydrolysis using Alcalase or Trypsin combined with Flavourzyme, we produced various hydrolysates, which were then fractionated via ultrafiltration. Using a combination of peptidomics and bioinformatics, we predicted the presence of metal-chelating and free radical scavenging peptides across all hydrolysate fractions, with a trend indicating a higher content of antioxidant peptides in lower molecular weight fractions. To validate these predictions, we utilized Surface Plasmon Resonance (SPR) and a 9-day emulsion storage experiment. While SPR demonstrated potential in identifying antioxidant activity, it faced challenges in differentiating between hydrolysate fractions due to significant standard errors. In the storage experiment, all hydrolysates showed lipid oxidation inhibition, though not as effectively as EDTA. Remarkably, one fraction (AF13) was not significantly different (p < 0.05) from EDTA in suppressing hexanal formation. These results highlight SPR and peptidomics/bioinformatics as promising yet limited methods for antioxidant screening. Importantly, this study reveals the potential of potato protein hydrolysates as antioxidants in food products, warranting further research.

Results from an explorative study revealing spatio-temporal patterns of the SARS-CoV-2/COVID-19 epidemic in Germany are presented. We dispense with contestable model assumptions and show the intrinsic spatio-temporal patterns of the epidemic dynamics. The analysis is based on COVID-19 incidence data, which are age-stratified and spatially resolved at the county level, provided by the Federal Government’s Public Health Institute of Germany (RKI) for public use. Although the 400 county-related incidence time series show enormous heterogeneity both with respect to temporal features as well as spatial distributions, the counties’ incidence curves organise into well distinguished clusters that coincide with East and West Germany. The analysis is based on dimensionality reduction, multidimensional scaling, network analysis, and diversity measures. Dynamical changes are captured by means of difference-in-difference methods which are related to fold changes of the effective reproduction numbers. The age-related dynamical patterns suggest a considerably stronger impact of children, adolescents and seniors on the epidemic activity than previously expected. Besides these concrete interpretations, the work mainly aims at providing an atlas for spatio-temporal patterns of the epidemic which serves as a basis to be further explored with the expertise from different disciplines, particularly sociology and policy makers. The study should also be understood as a methodological contribution to getting a handle on the unusual complexity of the COVID-19 pandemic.

Dynamic variables in the non-equilibrium systems of life are determined by catalytic activities. These relate to the expression of the genome. The extent to which such a variable depends on the catalytic activity defined by a gene has become more and more important in view of the possibilities to modulate gene expression or intervene with enzyme function through the use of medicinal drugs. With all the complexity of cellular systems biology, there are still some very simple principles that guide the control of variables such as fluxes, concentrations, and half-times. Using time-unit invariance we here derive a multitude of laws governing the sums of the control coefficients that quantify the control of multiple variables by all the catalytic activities. We show that the sum of the control coefficients of any dynamic variable over all catalytic activities is determined by the control of the same property by time. When the variable is at a maximum, minimum or steady, this limits the sums to simple integers like 0, -1, 1, and -2, depending on the variable under consideration. Some of the implications for biological control are discussed as is the dependence of these results on the precise definition of control.

The Kwee van Woerden (KvW) method for the determination of eclipse minimum times has been a staple in eclipsing binary research for decades, due its simplicity and independence of external input parameters. However, its estimates of the timing error have been known to be of low reliability. During the analysis of very precise photometry of CM Draconis eclipses from TESS space mission data, KvW’s original equation for the timing error estimate produced numerical errors, which evidenced a fundamental problem in this equation. This contribution introduces an improved way to calculate the timing error with the KvW method. A code that implements this improved method, together with several further updates over the original method is presented as well. An example application on the CM Draconis light curves from TESS is given, where we show that its timing error estimates of about 1 second are in excellent agreement with error estimates obtained by other means.

Accidents between right-turning commercial vehicles and crossing vulnerable road users (VRU) in urban environments often lead to serious or fatal injuries and therefore play a significant role in forensic accident analysis. To reduce the risk of accidents, blind spot assistance systems have been installed in commercial vehicles for several years, among other things, to detect VRUs and warn the driver in time. However, since such systems cannot reliably prevent all turning accidents, an investigation by experts must clarify how the accident occurred and to what extent the blind spot assistance system influenced the course of the accident. The occurrence of the acoustic warning message can be defined as an objective reaction prompt for the driver, so that the blind spot assistance system can significantly influence the avoidability assessment. In order to be able to integrate the system into forensic accident analysis, a precise knowledge of how the system works and its limitations is required. For this purpose, tests with different systems and accident constellations were conducted and evaluated. It was found that the type of sensor used for the assistance systems has a great influence on the system’s performance. The lateral distance between the right side of the commercial vehicle and the VRU as well as obstacles between them and the speed difference can take great influence on the reliability of the assistance system. Depending on the concrete time of the system’s warning signal the accident can be avoided or not by the driver when reacting on this signal.

Objective: To investigate postacute laryngeal injuries and dysfunctions (PLID) in coronavirus disease 2019 (COVID-19) patients. Methods: Three independent investigators performed a systematic review of the current literature studying PLID in patients with a history of COVID-19. The review was performed according to PRISMA Statement. Epidemiological, clinical, hospitalization features, laryngeal diseases and voice outcomes were extracted from the included papers. Results: Eight papers met our inclusion criteria (393 patients) corresponding to 5 uncontrolled prospective and 3 retrospective studies. The most prevalent PLID were vocal fold dysmotility (65%), vocal fold edema (35%), laryngopharyngeal reflux (21%), and muscle tension dysphonia (21%). Posterior glottic stenosis (12%), granuloma (14%), and posterior glottic diastasis (12%) were the most common injuries. Most patients with PLID were obese and had a history of intensive care unit hospitalization, and orotracheal intubation. The delay between the discharge and the laryngology office consultation ranged from 51 to 122 days. The mean duration of intubation ranged from 10 to 34 days. Seventy-eight (49%) intubated patients were in prone position. The proportion of patients requiring surgical treatment ranged from 39% to 70% (mean=48%). There was an important heterogeneity between studies about inclusion, exclusion criteria and outcomes. Conclusion: COVID-19 appeared to be associated with PLID, especially in patients with a history of intubation. However, future controlled studies are needed to evaluate if intubated COVID-19 patients reported more frequently PLID than patients who were intubated for other conditions.

The closed forms of the non-resonant thermonuclear function in the Maxwell-Boltzmann and Tsallis case with depleted tail are obtained in generalized special functions. The results are written in terms of H-function of two variables. The importance of the results in this paper lies in the fact that the reaction rate probability integrals in Maxwell-Boltzmann and Tsallis cases are not obtained by the conventional method of approximation or by means of a single variable transform technique but by means of a two variable transform method. The Behaviour of the depleted non-resonant thermonuclear functions are examined using graphs. The results in the paper are of much interest to astrophysicists and statisticians in their further work in this area.

Technical components should be produced sustainably and are subject to growing demands in terms of durability and reliability. To meet these expectations, the development of thermochemical processes is auspicious. Titanium alloys, which have a comparatively high gas solubility, allow temporary hydrogen (H) loading, often called thermo hydrogen treatment (THT). THT causes lattice deformation and reduces the β transformation temperature. These effects enable an adjustment of the microstructure, which improves the mechanical properties as compared to those produced conventionally. Furthermore, the process is applicable to complex geometries that cannot be surface hardened by mechanical surface treatment techniques. The investigation presented intends to realize a local microstructure gradient in additively via laser-powder bed fusion (L-PBF) manufactured cylindrical Ti–6Al–4V specimens by changing the distribution and morphology of strengthening precipitates as well as the β grain size depending on the distance to the surface, which should improve the material fatigue properties. To evaluate the mechanical properties of such THT-induced microstructure gradients, the resulting change in fatigue life in the LCF and HCF range was determined by stress-controlled cyclic deformation tests. Besides, the resulting microstructure was characterized by means of XRD and TEM. In addition to the additively manufactured and thermo hydrogen treated cylindrical specimens, conventionally produced tube-like specimens were thermo hydrogen treated and examined. For the THT-induced microstructure gradients, numerically simulated H concentration profiles as well as experimentally determined hardness profiles were used for the evaluation of the THT process. The study shows that H-loading at 500°C and H-degassing at 750°C, followed by aging at 550°C, allows the establishment of a microstructure gradient that shows an 8% improvement in fatigue properties compared to a reference condition without THT. The reason for this improvement is an increased volume fraction secondary alpha phase in the near-surface area of the specimens. Moreover, the results show that the process is applicable a tube-like specimen with varying wall thicknesses.

Based on comprehensible non-parametric methods, estimates of crucial parameters that characterise the COVID-19 pandemic with a focus on the German epidemic are presented. Where appropriate, the estimates for Germany are compared with the results for seven other countries (FR, IT, US, UK, ES, CH, BR) to get an idea of the breadth of applicability and a relational understanding. Thereby, only prevalence data of daily reported new counts of diagnosed cases and fatalities provided by the Johns Hopkins University are used. Drawing on uncertain a priori knowledge is avoided. Specifically, we present estimates resulting from delay-time correlations for the duration from diagnosis to death being 13 days for Germany and Switzerland. The delay-time correlation applied to time series from other countries exhibit less pronounced peaks suggesting high variabilities for the corresponding time-to-death durations. With respect to the German data, the two time series of new cases and fatalities exhibit a strong coherence within the frequency range of interest, which backs our findings. Furthermore, based on the knowledge of this time lag between diagnoses and deaths, properly delayed asymptotic as well as instantaneous fatality-case ratios are calculated having superiority compared to the commonly published case-fatality rate. The temporal median of the instantaneous fatality-case ratio with proper delay of 13-days between cases and deaths for Germany turns out to be 0.02. Time courses of asymptotic fatality-case ratios are presented for other countries which substantially differ during the first half of the pandemic, however, converge to a narrow range with standard deviation 0.57% and mean 2.4%. Additionally, the time courses of instantaneous fatality-case ratios with optimal delay for the 8 exemplarily chosen countries are calculated and compared by means of the temporal medians. Similarly to the asymptotic fatality-case ratios, the differences are much smaller than expected from mass media reports. The basic reproduction number, R₀, for Germany is estimated to be between 2.4 and 3.4. The uncertainty stems from uncertain knowledge of the generation time. A delay autocorrelation shows resonances at about 4 days and 7 days, where the latter resonance is at least partially attributable to the sampling process with weekly periodicity. The calculation of the basic reproduction number is based on an evaluation of cumulative numbers of cases yielding time-dependent doubling times as an intermediate step. This allows to infer to the reproduction number during the early phase of onset of the epidemic. In a second approach, the instantaneous reproduction number is derived from the incident (counts of new) cases and allows, in contrast to the first version, to infer to the temporal behaviour of the reproduction number during the later epidemic course. The time course of the reproduction number is compared to an alternative control measure given by the per capita growth, which largely confirms the conclusions drawn from the reproduction number. To conclude, by avoiding complicated parametric models we provide insights into basic features of the COVID-19 epidemic in an utmost transparent and comprehensible way. The perhaps most striking insight is that the fatality-case ratios do not differ between countries as much as previously suspected.

Deep eutectic solvents are a mixture of two or more components, that at a particular composition become liquids at room temperature. When the compounds that constitute the DES are primary metabolites, namely, amino acids, organic acids, sugars, or choline derivatives, the DES are so called natural deep eutectic solvents (NADES). NADES fully represent green chemistry principles. These solvents are highly welcome, as they are obtained from renewable resources, and gratifyingly biodegradable and biocompatible. They are an alternative to room temperature ionic liquids (RTILs). From the pharmaceutical industry point of view, they are highly desirable, but unfortunately have been rarely used despite their enormous potential. In this review, we will look at their impact on the asymmetric catalytic synthesis of key target molecules, via metal-based catalysis, biocatalysis and organocatalysis. In many cases the NADES that have been used are chiral and can even promote enantioselective reactions, this crucial and very exciting aspect will also be discussed and analysed.

Genetic and sporadic forms of tauopathies, the most prevalent of which is Alzheimer’s Disease, are a scourge of the aging society, and in case of genetic forms, can also affect children and young adults. All tauopathies share ectopic expression, mislocalization, or aggregation of the microtubule associated protein TAU, encoded by the MAPT gene. As TAU is a neuronal protein widely expressed in the CNS, the overwhelming majority of tauopathies are neurological disorders. They are characterized by cognitive dysfunction often leading to dementia, and are frequently accompanied by movement abnormalities such as parkinsonism. Tauopathies can lead to severe neurological deficits and premature death. For some tauopathies there is a clear genetic cause and/ or an epigenetic contribution. However, for several others the disease etiology is unclear, with few tauopathies being environmentally triggered. Here we review current knowledge of tauopathies listing known genetic and important sporadic forms of this disease. Further, we discuss how DNA methylation as a major epigenetic mechanism emerges to be involved in the disease pathophysiology of Alzheimer’s, and related genetic and non-genetic tauopathies. Finally, we debate the application of epigenetic signatures in peripheral blood samples as diagnostic tool and usage of epigenetic therapy strategies for these diseases.

We present our experience with the implantation of flow diverter stents (FDSs) for the management of intern carotid artery (ICA) dissections in tortuous tonsillar loop segments. 16 patients (10 women, 62.5%; mean age 39±8 years; median baseline NIHSS 13; median ASPECTS 8.5) with acute ischemic stroke due to ICA dissection in a tortuous tonsillar loop segment, with/without large intracranial vessel thrombotic occlusion, from 6/2015−2/2022 were included in this retrospective study under a waiver of informed consent. An FDS device was deployed from the petrous ICA toward the upper cervical ICA, completely covering the tonsillar loop. Stentriever-assisted thrombectomy was performed when indicated. A dual antiplatelet regimen was used during and after the procedure. Thrombocyte inhibition levels were evaluated before, during, and after the intervention. The ICA occlusion/near occlusion was successfully recanalized in all 16 patients with postangioplasty residual stenosis of 34±14% (range 0−50%). Stent-assisted embolectomy was performed in 15/16 patients (93.7%), achieving revascularization (TICI 2b−3) in all. There were no procedural complications and no intraprocedural embolic events; one asymptomatic petechial hemorrhage was detected. At 3-month follow-up, mRS 0−2 was seen in all patients. This report provides pilot data for a subsequent study on the use of flow diverter stents for ischemic cerebrovascular conditions. Our encouraging preliminary results await confirmation from further experience and prospective randomized studies.

System-of-systems (SoS) approach is often used for simulating disruptions to business and infrastructure system networks allowing for integration of several models into one simulation. However, the integration is frequently challenging as each system is designed individually with different characteristics, such as time granularity. Understanding the impact of time granularity on propagation of disruptions between businesses and infrastructure systems and finding the appropriate granularity for the SoS simulation remain as major challenges. To tackle these, we explore how time granularity, recovery time, and disruption size affect the propagation of disruptions between constituent systems of an SoS simulation. To address this issue, we developed a High Level Architecture (HLA) simulation of 3 networks and performed a series of simulation experiments. Our results revealed that time granularity and especially recovery time have huge impact on propagation of disruptions. Consequently, we developed a model for selecting an appropriate time granularity for an SoS simulation based on expected recovery time. Our simulation experiments show that time granularity should be less than 1.13 of expected recovery time. We identified some areas for future research centered around extending the experimental factors space.

The microtubule-associated protein TAU is sorted into the axon in healthy brain neurons. Somatodendritic missorting of TAU is a pathological hallmark of many neurodegenerative diseases called tauopathies, including Alzheimer’s Disease (AD). Cause, consequence, and (patho)physiological mechanisms of TAU sorting and missorting are understudied, in part also due to the lack of readily available human neuronal model systems. The human neuroblastoma cell line SH-SY5Y is widely used for studying TAU physiology and TAU-related pathology in AD and related tauopathies. SH-SY5Y cells can be differentiated into neuron-like cells (SH-SY5Y-derived neurons) using various substances. This review evaluates whether SH-SY5Y-derived neurons are a suitable model for i) investigating intracellular TAU sorting in general, and ii) with respect to neuron subtype-specific TAU vulnerability. I) SH-SY5Y-derived neurons show pronounced axodendritic polarity, high levels of axonally localized TAU protein, expression of all six major human brain isoforms, and TAU phosphorylation similar to the human brain. As proliferative cells, SH-SY5Y cells are readily accessible for genetic engineering, stable transgene integration and leading-edge genome editing are valuable and promising tools for TAU-related studies. II) Depending on the used differentiation procedure, SH-SY5Y-derived neurons resemble cells of distinct subcortical nuclei, i.e. the Locus coeruleus (LC), Nucleus basalis (NB) and Substantia nigra (SN), all of which early affected in many tauopathies. This allows to analyse neuron-specific TAU isoform expression and intracellular localization, also in the context of vulnerability to TAU pathology. Limitations are e.g. the lack of mimicking age-related tauopathy risk factors and the difficulty to define the exact neuronal subtype of SH-SY5Y-derived neurons. In brief, this review discusses the suitability of SH-SY5Y-derived neurons for investigating TAU (mis)sorting mechanisms and neuron-specific TAU vulnerability in disease paradigms.

Translation of basic animal research to find effective methods of diagnosing and treating human neurological disorders requires parallel analysis infrastructures. Small animals such as mice provide exploratory animal disease models. However, many interventions developed using small animal models fail to translate to human use due to physical or biological differences. Recently, large-animal minipigs have emerged in neuroscience due to both brain similarity and economic advantages. Medical image processing is a crucial part of research as it allows researchers to monitor their experiments and understand disease development. However, although many algorithms are created and optimized for MR analysis of human data, those tools are not directly applicable or sufficiently sensitive to measure minipig data. In this work, we propose PigSNIPE - a pipeline for the automated handling, processing, and analyzing of large-scale data sets of minipig MR images. The pipeline allows for image registration, AC-PC alignment, landmark detection, skull stripping, brainmasks and intracranial volume segmentation (DICE 0.98), tissue segmentation (DICE 0.82), and caudate-putamen brain segmentation (DICE 0.8) in under two minutes. To the best of our knowledge, this is the first automated pipeline tool aimed at large animal images.

The transportation sector significantly contributes to greenhouse gas emissions, thus imposing sig-nificant environmental hazards. In response, many nations have begun promoting Electric Vehicles (EVs) as an ecologically sustainable substitute for traditional combustion vehicles. Lithium-Ion Batteries (LIBs), characterized by their high energy density, extended lifespan, and relatively low self-discharge rate, have become the suitable energy storage system for EVs, advancing the field of sustainable transportation. The decreasing cost of LIB production has primarily driven this progression, realized through a combination of economies of scale, advancements in electrode materials and cell design, and re-finements in manufacturing processes. All these elements collectively contribute to the cost reduc-tion of LIBs. A foreseeable implication of this trend is an expected surge in LIBs that will exhaust their operational lifespan and, consequently, be cast away into the environment. One mitigating strategy for this impending environmental issue involves collecting these spent EV batteries, re-configuring them, and repurposing them for applications with less rigorous weight, performance, and size prerequisites. This approach would not only prolong the utility life of the batteries but also ameliorate their environmental impacts. Nevertheless, second-life batteries are anticipated to exhibit a higher rate of gas evolution, necessitating comprehensive testing and readjustments to ensure safe operation in secondary ap-plications. The regulatory framework encompassing the second-life battery sector still needs to be defined regarding norms, technical standards, and legislation. This paper aims to elucidate the primary regulations and technical standards proposed thus far in the second-life battery marketplace. The results underscore the exigency for neutral evaluative entities, such as universities, research centers, and governmental institutions, to perform an unbi-ased assessment of the second-life battery market. This would pave the way for novel technical standards and legislative measures specifically tailored to this emerging sector.

The tetracyclic pyrido[4,3-b]carbazole olivacine and four of its oxygenated derivatives have been synthesized by a late-stage palladium-catalyzed Heck-type cyclization of the pyrrole ring as key step. In a test for inhibition of the growth of Mycobacterium tuberculosis 9-methoxyolivacine showed the most significant inhibiting activity against Mycobacterium tuberculosis with an MIC₉₀ value of 1.5 μM.

Protein hydrolysates show great promise as bioactive food and feed ingredient and for valorization of side-streams from e.g. the fish processing industry. This study characterizes bulk emulsifying, foaming, and in vitro antioxidative properties of hydrolysates derived from cod frame by application of Alcalase and Neutrase, individually and sequentially as well as the influence of heat-treatment prior to hydrolysis. We present a novel approach that utilizes proteomics data for calculation of weighted mean peptide properties (length, molecular weight, and charge) and peptide-level abundance estimation. Using subsequent bioinformatic prediction of biofunctional properties to describe observed bulk properties, we are able to provide an in-depth hydrolysate characterization not previously seen. All hydrolysates displayed comparable or higher emulsifying activity and stability than sodium caseinate. Heat-treatment significantly increased stability but showed a negative effect on the activity and degree of hydrolysis. Combining peptide abundance with predicted emulsifying activity, we were able to identify several peptides that are likely linked to the observed differences in bulk emulsifying properties. In general, decreased hydrolysis resulted in significantly higher chelating activity, while the opposite was observed for radical scavenging activity. The study highlights the prospects of applying proteomics and bioinformatics for hydrolysate characterization and in food protein science.

The inherent dependency of deep learning models to labeled data is a well-known problem and one of the barriers that slows down the integration of such methods into different fields of applied sciences and engineering, in which experimental and numerical methods can easily generate a colossal amount of unlabeled data. This paper proposes an unsupervised domain adaptation methodology that mimics the peer review process to label new observations in a different domain from the training set. The approach evaluates the validity of a hypothesis using domain knowledge acquired from the training set through a similarity analysis, exploring the projected feature space to examine the class centroid shifts. The methodology is tested on a binary classification problem, where synthetic images of cubes and cylinders in different orientations are generated. The methodology improves the accuracy of the object classifier from 60% to around 90% in the case of a domain shift in physical feature space without human labeling.

Detector-based spectral CT offers the possibility of obtaining spectral information from which discrete acquisitions at different energy levels can be derived, yielding so-called virtual monoenergetic images (VMI). In this study, we aimed to develop a jointly optimized deep learning framework based on dual-energy CT pulmonary angiography (DE-CTPA) data to generate synthetic monoenergetic images (SMI) for improving automatic pulmonary embolism (PE) detection in single-energy CTPA scans. For this purpose, we used two data sets: our institutional DE-CTPA data set D1 comprising polyenergetic arterial series and the corresponding VMI at low-energy levels (40 keV) with 7,892 image pairs, and a 10% subset of the 2020 RSNA Pulmonary Embolism Detection Challenge data set D2, which consisted of 161,253 polyenergetic images with dichotomous slice-wise annotations (PE/no PE). We trained a fully convolutional encoder-decoder on D1 to generate SMI from single-energy CTPA scans of D2, which were then fed into a ResNet50 network for training of the downstream PE classification task. The quantitative results on the reconstruction ability of our framework revealed high-quality visual SMI predictions with reconstruction results of 0.984 ± 0.002 (structural similarity) and 41.706 ± 0.547 dB (peak-signal-to-noise ratio). PE classification resulted in an AUC of 0.84 for our model, which achieved improved performance compared to other naive approaches with AUCs up to 0.81. Our study stresses the role of using joint optimization strategies for deep learning algorithms to improve automatic PE detection. The proposed pipeline may prove to be beneficial for computer-aided detection systems and could help rescue CTPA studies with suboptimal opacification of the pulmonary arteries from single-energy CT scanners.

Current clinical treatment options for symptomatic, partial-thickness rotator cuff tear (sPTRCT) offer only limited potential for true tissue healing and improvement of clinical results. In animal models, injections of adult stem cells isolated from adipose tissue into tendon injuries evidenced histological regeneration of tendon tissue. However, it is unclear whether such beneficial effects could also be observed in a human tendon treated with fresh, uncultured, autologous, adipose derived regenerative cells (UA-ADRCs). A specific challenge in this regard is that UA-ADRCs cannot be labeled and, thus, not unequivocally identified in the host tissue. Therefore, histological regeneration of injured human tendons after injection of UA-ADRCs must be assessed using comprehensive, immunohistochemical and microscopic analysis of biopsies taken from the treated tendon a few weeks after injection of UA-ADRCs.

With the advent of real-time MRI, the motion and passage of cerebrospinal fluid can be visualized without gating and exclusion of low-frequency waves. This imaging modality gives insights into low-volume, rapidly oscillating cardiac-driven movement as well as sustained, high-volume, slowly oscillating inspiration-driven movement.Inspiration means a spontaneous or artificial increase in the intrathoracic dimensions independent of body position. Alterations in thoracic diameter enable the thoracic and spinal epidural venous compartments to be emptied and filled, producing an upward surge of cerebrospinal fluid inside the spine during inspiration; this surge counterbalances the downward pooling of venous blood toward the heart.Real-time MRI, as a macroscale in vivo observation method, could expand our knowledge of neurofluid dynamics, including how astrocytic fluid preloading is adjusted and how brain buoyancy and turgor are maintained in different postures and zero gravity.Along with these macroscale findings, new microscale insights into aquaporin-mediated fluid transfer, its sensing by cilia and its tuning by nitric oxide will be reviewed. By incorporating clinical knowledge spanning several disciplines, certain disorders—congenital hydrocephalus with Chiari malformation, idiopathic intracranial hypertension and adult idiopathic hydrocephalus—are interpreted and reviewed according to current concepts, from the basics of the interrelated systems to their pathology.

We present a method to study the interannual variability of the annual cycle. The method consists of first determining the amplitude and phase of segments of 12 monthly means at all spatial points, resulting in one complex number per grid point and per year. The complex fields, once per year, are then subject to a complex EOF (CEOF) analysis. We consider as an example the barotropic stream function in the South China Sea as simulated with an ocean general circulation model across 6 decades of years, driven my realistic (NCEP) weather forcing. We find 3 to 4 to “significant” CEOFs, which account for about 53 to 62% of variance. These CEOFs go with large-scale patterns. Their time coefficients are mostly stationary, but point to some inhomogeneities related to instationarities in the forcing. In particular, the simulation since 1950-1958 deviates from the remainder of the simulation. The first CEOF describes variations in the center of the South China Sea. Its principal component describes a systematic, albeit noisy shift by almost 180o from 1960 to about the year 2000. When overlaid the long-term mean annual mean, the overall change consists of an amplification of the annual cycle in the 1960s and 1990s, whereas In the 1970s, the amplitude was reduced. Phase shifts in the anomaly (given by the CEOFs) have a small effect, because of the dominance of the mean annual cycle. These variations are not related to ENSO variability but may origin in variations of the Southeast monsoon. The second EOF represents strong changes, both in terms of intensity and phase, in the Luzon strait.

Estimating the remaining useful life (RUL) of components is a crucial task to enhance the reliability, safety, productivity, and to reduce maintenance cost. In general, predicting the RUL of a component includes constructing a health indicator ( ) to infer the current condition of the component, and modelling the degradation process, to estimate the future behavior. Although many signal processing and data-driven based methods were proposed to construct the , most of the existing methods are based on manual feature extraction techniques, and need the prior knowledge of experts, or rely on a large amount of failure data. Therefore, in this study, a new data-driven method based on the convolutional autoencoder (CAE) is presented to construct the . For this purpose, the continuous wavelet transform (CWT) technique is used to convert the raw acquired vibrational signals into a two-dimensional image; then, the CAE model is trained by the healthy operation dataset. Finally, the Mahalanobis Distance (MD) between the healthy and failure stages is measured as the . The proposed method is tested on a benchmark bearing dataset and compared with several other traditional construction models. Experimental results indicate that the constructed exhibits a monotonically increasing degradation trend and has a good performance to detect incipient faults.

The main objective of this communication is to describe the ‘Global Salt Cycle’. Giant salt accumulations are commonly found along continental margins of former rifts. The first stage in the accumulation process is saturation of newly formed oceanic crust with seawater. Final mobilisation and accumulation of the salts occurs during rifting, localised in the vicinity of relict subduction zones. Oceanic crust is created along the spreading ridges in the deep oceans of the Earth. It exchanges mass and energy with seawater in hydrothermal circulation cells that penetrate deep into the new and fractured crust. Water-rock interactions include the formation of hydrated and hydroxylated minerals, e.g., serpentinites and clay minerals. By incorporating hydroxyl groups and water in their crystal lattices, the salinity of remaining brines increases. Subduction of oceanic crust and serpentinised lithosphere transports water, hydrated minerals, and marine salts deep into the crust and mantle. Upon pressurisation and heating of the subducting slab, different parts of this water are expelled at different depths/temperatures. The resulting fluids will contain salts brought in with the slab, as well as new salts formed by water-rock interaction. The combination of elevated pressures and temperatures, water, salinity, and CO2, create permeability in the normally impermeable, peridotitic mantle, by altering the fluid-rock dihedral angles of mineral grains. This P/T-determined intergranular permeability allows ascent of saline fluids, under lithostatic pressure, within the mantle wedge, or the slab itself. The fluids produce a mechanically weakened and buoyant zone within the mantle wedge due to high pore pressure between mineral grains and reduced mantle density. During the lifetime of a subduction zone, a substantial accumulation of saline fluids within the mantle wedge and crust, is evident. Deep, fluid reservoirs accumulate between the subduction trench and the volcanic front. They may exist for hundreds of millions of years, even after the extinction of the subduction zone. Saline fluids may escape to the surface along deep faults, due to overfilling of available pores/fractures. Fluids within the mantle wedge may form rock melts or exist as supercritical, mineral rich fluids. The combination of reduced pressure due to rifting, and a saline and buoyant mantle, creates a mantle circulation that brings the accumulated, saline fluids, to crustal levels. Salts will therefore accumulate during initial stages of rifting as a result of massive fluid expulsion, phase change and boiling of mantle fluids. No extra energy is required to produce phase change and boiling. The result is formation of solid salts or dense brines/slurries invading fractured crustal rocks, or escaping to the surface/seabed. This process may take place both before and after the sea has invaded a continental rift.

The astacin protease Meprin β represents an emerging target for drug development due to its potential involvement in disorders such as acute and chronic kidney injury and fibrosis. Here, we elaborate on the structural basis of inhibition by a specific Meprin β inhibitor. Our analysis of the crystal structure suggests different binding modes of the inhibitor to the active site. This flexibility is caused, at least in part, by movement of the C-terminal region of the protease domain (CTD). The CTD movement narrows the active site cleft upon inhibitor binding. Compared with other astacin proteases, among those the highly homologous isoenzyme Meprin α, differences in the subsites account for the unique selectivity of the inhibitor. Although the inhibitor shows substantial flexibility in the orientation within the active site, the structural data as well as binding analyses including molecular dynamics simulations support a contribution of electrostatic interactions, presumably by arginine residues, to binding and specificity. Collectively, the results presented here and previously support an induced fit and substantial movement of the CTD upon ligand binding and, possibly, during catalysis. To the best of our knowledge, we here present the first structure of a Meprin β holoenzyme containing a zinc ion and a specific inhibitor bound to the active site. The structural data will guide rational drug design and the discovery of highly potent Meprin inhibitors.

A large variety of fermentation products are used in food and feed production, but also in other industries, and many of these products are produced with genetically modified microorganisms (GMMs). In food and feed production, prominent examples are amino acids, vitamins, food and feed enzymes, colorants, non-caloric sweeteners and human milk oligosaccharides. From a regulatory perspective, fermentation products are typically produced under containment. This means that premises, equipment and work processes need to be designed to prevent or at least minimize release of GMMs into the environment. The fermentation products themselves should not contain any live cells of the GMM. Over the past years, there have been concerning developments, particularly in the European Union, stipulating that also absence of recombinant DNA might be interpreted as a regulatory requirement for fermentation products produced with GMMs. In this paper, we (i) attempt to place these developments into the historical context, (ii) sketch the potential negative repercussions for the food and feed industries, (iii) elaborate on the safety of recombinant DNA, and (iv) postulate that recombinant DNA should remain an integral part of the safety assessment of fermentation products but should not be misconstrued as a criterion for regulatory classification of products of biotechnology.

The determination of crack propagation velocities can provide valuable information for a better understanding of damage processes of concrete. The spatio-temporal analysis of crack patterns developing at a speed of several hundred meters per second is a rather challenging task. In the paper, a photogrammetric procedure for the determination of crack propagation velocities in concrete specimens using high-speed camera image sequences is presented. A cascaded image sequence processing which starts with the computation of displacement vector fields for a dense pattern of points on the specimen’s surface between consecutive time steps of the image sequence chain has been developed. These surface points are triangulated into a mesh, and as representations of cracks, discontinuities in the displacement vector fields are found by a deformation analysis applied to all triangles of the mesh. Connected components of the deformed triangles are computed using region-growing techniques. Then, the crack tips are determined using principal component analysis. The tips are tracked in the image sequence and the velocities between the time stamps of the images are derived. A major advantage of this method as compared to established techniques is in the fact of its allowing for spatio-temporally resolved, full-field measurements rather than point-wise measurements and that information on crack width can be obtained simultaneously. To validate the experimentation, the authors processed image sequences of tests on four compact-tension specimens performed on a split-Hopkinson tension bar. The images were taken by a high-speed camera at a frame rate of 160,000 images per second. By applying to these datasets the image sequence processing procedure as developed, crack propagation velocities of about 800 m/s were determined with a precision in the order of 50 m/s.

Malassezia is a lipid-dependent genus of yeasts known for being an important part of the skin mycobiota. These yeasts have been associated in the development of skin disorders and cataloged as a causal agent of systemic infections under specific conditions, making them opportunistic pathogens. Little is known about the host-microbe interaction of Malassezia spp., and unraveling this implies the implementation of infection models. In this mini review we present different models that have been implemented in the fungal infections study with greater attention in Malassezia spp. infections. These models range from in vitro (cell cultures and ex vivo tissue), to in vivo (murine models, rabbits, guinea pigs, insects, nematodes, and amoebas). We additionally highlight the alternative models that reduce the use of mammals as model organisms, which have been gaining importance in the study of fungal host-microbe interactions. This is due to the fact that these systems have shown to have reliable results, which correlate with those obtained from mammalian models. Example of alternative models are Caenorhabditis elegans, Drosophila melanogaster, Tenebrio molitor, and Galleria mellonella. These are invertebrates that have been implemented in the study of Malassezia spp. infections in order to identify differences in virulence between Malassezia species.

We review the state of dynamical downscaling with scale-constrained regional and global models. The methodology, in particular spectral nudging, has become a routine and well-researched tool for hindcasting climatologies of sub-synoptic atmospheric disturbances in coastal regions. At present, the spectrum of applications is expanding to other phenomena, but also to ocean dynamics and to extended forecasting. Also new diagnostic challenges are appearing such as spatial characteristics of small-scale phenomena such as Low Level Jets.

As a part of the European Green Deal, the Corporate Sustainable Reporting Directive will apply to over 50,000 companies in Europe, meant to advance the quality of sustainability reporting in the EU, and reduce global emissions and emission distribution inequality. Part of the requirements centre around organisational emission quantification, which will bring much attention to the methodological aspects and resulting decision support capability, which calls for synthesis and argues for clarity. Currently, quantifying the emissions embedded in global transactions mostly focus on direct value-chain attributes, and do not consider unintended consequences beyond the scope of assessment. To achieve genuine reductions, estimated emissions must be considered from a systems perspective to accurately reflect their true impact. While emission inventories serve several purposes, incorrect application limits their potential. The CSRD aligns itself with the GHG Protocol, which does not explicitly facilitate this distinction, although new Land Sector and Removals Guidance draft does, in part. With first CSRD reports expected in 2025, and the GHG protocol entering a revisions period, it presents an opportunity to marry systems thinking with carbon literacy, thereby equipping the expected surge of activity with the sufficient tools for an accelerated transition.

The objective of this pilot study was to compare glucose concentrations in capillary blood (CB) samples analysed in a laboratory by a validated method and glucose concentrations measured in the interstitial fluid (ISF) by continuous glucose monitoring under different physical activity levels in a postprandial state in healthy and active subjects without diabetes. Ten healthy, active subjects (26±4 years, 67±11 kg bodyweight (BW), 11±3 h) were included in the study. Within 14 days, they underwent six tests consisting of a) resting fasted (R/Fast), b) resting after intake of 1 g glucose/kg BW (R/Glc) and c) running for 60 minutes at moderate (65/Glc) and d) high (85/Glc) intensity after intake of 1 g glucose/kg BW. Data were collected in the morning, following a standardised dinner before test day. Sensor-based glucose concentrations were compared to simultaneous capillary blood glucose concentrations. Pearson’s r correlation coefficient was highest for R/Glc (.92, p<.001) compared to R/Fast (.45, p<.001), 65/Glc (.60, p<.001) and 85/Glc (.70, p<.001). Mean absolute relative deviation (MARD) and standard deviation (SD) was smallest for resting fasted and similar between all other conditions (R/Fast: 8±6%, R/Glc: 17±12%, 65/Glc: 22 ± 24%, 85/Glc: 18±17%). However, Bland-Altman plot analysis showed a higher range between lower and upper limits of agreement (95% confidence interval) of paired data under exercising compared to resting conditions. Under resting fasted conditions, both methods produce similar outcomes. Under resting postprandial and exercising conditions, respectively, there are differences between both methods. However, further data in healthy subjects need to be gathered considering physical activity and nutrition status.

In the context of Covid-19 virus containment, there is a lack of acceptance of preventive measures in the population. The present work investigated which factors influence the belief in of scientific propositions compared belief in conspiracy theories. The focus here was on the determinants of conspiracy beliefs in the context of Covid-19 related media content. Using an online questionnaire (N = 175), results indicate that scientific compared to conspiracy theoretical media content led to higher acceptance. Furthermore, Need for Cognition (NFC-K), a conspiracy theoretical worldview (CMQ), and openness to experience (NEO-FFI) were positively associated with conspiracy beliefs derived from Facebook postings. In addition, a conspiracy theoretical worldview was negatively associated with belief in scientific media content. Furthermore, agreeableness was unrelated to conspiracy beliefs, although it was positively associated with conspiracy theoretical worldview. The results imply promising persuasion strategies for reducing conspiracy theoretical beliefs and to increase the acceptance of preventive measures.

Multiple sclerosis is an autoinflammatory condition that results in damage of myelinated neurons in affected patients. While disease-modifying treatments have been successful in slowing the progression of relapsing remittent disease, most patients still progress to secondary progressive disease that is largely unresponsive to disease-modifying treatments. Similarly, there is currently no effective treatment for patients with primary progressive MS. Innate and adaptive immune cells in the CNS play a critical role in initiating an autoimmune attack and in maintaining the chronic inflammation that drives disease progression. In this review, we will focus on recent insights into the role of T cells with regulatory function in suppressing the progression of MS, and, more importantly, in promoting the remyelination and repair of MS lesions in the CNS. We will discuss the exciting opportunity to genetically reprogram regulatory T cells to achieve immune suppression and enhance repair locally at sites of tissue damage, while retaining a fully competent immune system outside the CNS. In the future, reprogramed regulatory T cells with defined specificity and function may provide life medicines that can persist in patients and achieve lasting disease suppression after one cycle of treatment.

To understand forest dynamics under today’s changing environmental conditions, it is important to analyze the state of forests at large scales. Forest inventories are not available for all regions, so it is important to use other additional sources of information, e.g. remote sensing observations. Increasingly, remotely sensed data based on optical instruments and airborne LIDAR are becoming widely available for forests. There is great potential in analyzing these measurements and gaining an understanding of forests state. In this work, we combine the new generation radiative transfer model mScope with the individual-based forest model FORMIND to generate reflectance spectra for forests. Combining the two models allows us to account for species diversity at different height layers in the forest. We compare the generated reflectances for forest stands in Finland, in the region of North Karelia, with Sentinel-2 measurements. We investigate which level of forest representation gives the best results. For the majority of the forest stands, we generated good reflectances with all levels forest representation compared to the measured reflectance. Good correlations were also found for the vegetation indices (especially NDVI with R²=0.62). This work provides a forward modelling tool for relating forest reflectance to forest characteristics. With this tool it is possible to generate a large set of forest stands with corresponding reflectances. This opens the possibility to understand how reflectance is related to succession and different forest conditions.

To remain relevant in the green transition, companies are beginning to voluntarily account for the exchange of emissions in their supply chain transactions and using the resulting greenhouse gas inventories for climate resilient decision support. Market advantages of sustainability and transparency see a shift from internal decision support tools to external communication tools which potentially expose companies to the risk of uncovering greenwashing if claims are not supported by transparent data, sound modelling, and a climate just emissions inventory, which considers external impacts connected to the production system. The different methods and standards in place for such greenhouse gas inventories, despite all referring to the ISO life cycle analysis standards and guidelines, present mixed signals and leave room for different interpretations, that may ultimately lead to cascading greenwashing, misleading results, and false successes. The new GHG Protocol Land Sector and Removals Guidance draft addresses this in part. With the GHG Protocol moving into revision periods, we identify gaps that present barriers to companies, or allow for interpretations that goes against the intentions of reporting GHG emissions related to an activity or organisation. The literature agrees that not rectifying these subtle-ties present counterproductive decision support for the green transition’s overall goal: to reduce global emissions.

Vaccine uptake is one of the indicators that has been used to guide immunization programs. This study aimed to evaluate whether the measles vaccine uptake is predicted by measles vaccine hesitancy. A community-based cross-sectional study was conducted in urban districts in Khartoum state in February 2019. Measles vaccine uptake among children was measured as either fully vaccinated or partially/not vaccinated. The Parents Attitude about Childhood Vaccination (PACV) scale was used to measure measles vaccine hesitancy. Multivariate logistic regression was run to identify the predictors of measles vaccination uptake controlling for sociodemographic variables and the adjusted odds ratios (aORs) with 95% CI were calculated. The receiver operator characteristic (ROC) curve was performed, besides area under the curve (AUC) for the PACV was computed. Data was collected from 495 participants. We found that measles vaccine hesitancy (PACV scores) predicted the uptake of measles vaccine after controlling other potential social confounders such as mother’s age and the number of children (aOR 1.055, 95% CI 1.028-1.028). Additionally, the ROC for the PACV yielded area under the curve (AUC 0.686 (95% CI 0.620-0.751, P <0.001). Our findings show that measles vaccine hesitancy in Sudan directly influences the uptake of the measles vaccine. Addressing the determinants of vaccine hesitancy through communication strategies will improve vaccine uptake.

Partially automated driving functions (SAE Level 2) can control a vehicle's longitudinal and lateral movements. However, taking over the driving task involves automation risks that the driver must manage. In severe accidents, the driver's ability to avoid a collision must be assessed, considering their expected reaction behavior. The primary goal of this study is to generate essential data on driver reaction behavior in case of malfunctions in partially automated driving functions for use in legal affairs. A simulator study with two scenarios involving 32 subjects was conducted for this purpose. The first scenario investigated driver reactions to system limitations during cornering. The second scenario examined driver responses to phantom braking caused by the AEBS. As a result, the first scenario shows that none of the subjects could control the situation safely. Due to partial automation, we could also identify a new part of the reaction time, the hands-on time, which leads to increased steering reaction times of 1.18 to 1.74 seconds. In the second scenario, we found that 25 of the 32 subjects could not override the phantom braking by pressing the accelerator pedal, although 16 subjects were informed about the system analog to the actual vehicle manuals. Overall, the study suggests that the current legal perspective on vehicle control and the expected driver reaction behavior for accident avoidance should be reconsidered.

In our study we investigated the additive manufacturing (AM) of ceramic-based Functionally Graded Materials (FGM) by the direct AM technology Thermoplastic 3D-Printing (T3DP). Zirconia components with a varying microstructure were additively manufactured by using thermoplastic suspensions with different contents of pore forming agents (PFA) and were co-sintered defect-free. Different materials were investigated concerning their suitability as PFA for the T3DP process. Different zirconia-based suspensions were prepared and used for AM of single- and multi-material test components. All samples were sintered defect-free and in the end we could realize a brick wall-like component consisting of dense (<1% porosity) and porous (approx. 5% porosity) zirconia areas to combine different properties in one component. The T3DP opens the door to AM of further ceramic-based 4D-components like multi-color or multi-material, especially multi-functional components.

Mild Cognitive Impairment (MCI) may progress to severe forms of dementia, so therapy is needed to maintain cognitive abilities. The neural circuitry for oculomotor control is closely linked to that which controls cognitive behavior. In this study, we tested whether training the oculomotor system with gaze-controlled video games could improve cognitive behavior in MCI patients. Patients played a simple game for a month while a control group played the same game using a mouse. Cognitive improvement was assessed using the MoCA screening test and CANTAB. We also measured eye pupil and vergence responses in an oddball paradigm. The results showed an increased score on the MoCA test specifically for the visuospatial domain and on the Rapid Visual Information Processing test of the CANTAB battery. Pupil responses also increased to target stimuli. Patients in the control group did not show significant improvements. This pilot study provides evidence for the potential cognitive benefits of gaze-controlled gaming in MCI patients.

Future cyber-physical systems may extend over broad geographical areas, like cities or regions, thus requiring the deployment of large real-time networks. A strategy to guarantee predictable communication over such networks is to synthesize an offline time-triggered communication schedule. However, this synthesis problem is computationally hard (NP-complete), and existing approaches do not scale satisfactorily to the required network sizes. This article presents a segmented offline synthesis method which substantially reduces this limitation, being able to generate time-triggered schedules for large hybrid (wired and wireless) networks. We also present a series of algorithms and optimizations that increase the performance and compactness of the obtained schedules while solving some of the problems inherent to segmented approaches. We evaluate our approach on a set of realistic large-size multi-hop networks, significantly larger than those considered in the existing literature. The results show that our segmentation reduces the synthesis time up to two orders of magnitude.

Pure orbital blowout fractures occur within the confines of the internal orbital wall. Restoration of orbital form and volume is paramount to prevent functional and esthetic impairment. The anatomical peculiarity of the orbit has encouraged surgeons to develop implants with customized features to restore its architecture. This has resulted in worldwide clinical demand for patient-specific implants (PSIs) designed to fit precisely in the patient's unique anatomy. Fused filament fabrication (FFF) three-dimensional (3D) printing technology has enabled the fabrication of implant-grade polymers such as Polyetheretherketone (PEEK), paving the way for a more sophisticated generation of biomaterials. This study evaluates the FFF 3D printed PEEK orbital mesh customized implants with a metric considering the relevant design, biomechanical, and morphological parameters. The performance of the implants is studied as a function of varying thicknesses and porous design constructs through a finite element (FE) based computational model and a decision matrix based statistical approach. The maximum stress values achieved in our results predict the high durability of the implants, and the maximum deformation values were under one-tenth of a millimeter (mm) domain in all the implant profile configurations. The circular patterned implant (0.9 mm) had the best performance score. The study demonstrates that compounding multi-design computational analysis with 3D printing can be beneficial for the optimal restoration of the orbital floor.

Proposal: Pineal region cysts (PCs) may affect the tectum and aqueduct and cause deep central vein congestion and endocrine dysfunction. In addition to headaches, PC often causes a broad range of symptoms, leading to prolonged diagnosis and therapy. The aims of this study are to reveal parameters that might explain the ambiguity of the symptoms and to identify factors association with the respiration driven neurofluid preload system. Methods: This retrospective study included 28 paediatric patients (mean age 11.6 years) who received surgical treatment for pineal region cysts and 18 patients (mean age 11.3 years) who were followed conservatively. Multiple clinical patient characteristics, such as symptoms, time to neuroimaging diagnosis, cyst size, ventricular indices, head circumference and postoperative outcome, were analysed. Four patients were investigated for CSF dynamics with real-time MRI. The mean follow-up time was 1.6 years. Results: The most common early onset symptoms were headaches (92%), blurred vision (42.8%), sleep disturbances (39.3%) and vertigo (32.1%). Tectum contact was observed in 82% of patients, and MRI examinations revealed that imaging flow void signals were absent in 32.1% of patients. The mean cyst diameters were 13.7 mm for the axial axis and 15.6 mm for the longitudinal axis. Together with a postoperative flow void signal, 4 patients recovered their respiration-driven CSF upward flow, which was not detectable before OP. After operation in 92.1% of patients, the leading symptoms improved without any mortality or morbidity. Conclusion: Despite proximity to the tectum and aqueduct with frequently absent aqueductal flow void signals, hydrocephalic ventricular enlargement was never detected. Data from real-time MRI depicted a reduced preoperative filling of the ventricular CSF compartments, indicating a diminished fluid preload, which recovered postoperatively.

Purpose: ETV is indicated for treating obstructions of major CSF pathways. The outcome evaluation often yields success rates of only +- 70% for shunt independency. Hence, compromised CSF absorption seems to occur more often than expected. We searched for parameters suitable to assess the involved CSF dynamics. Material and Methods: This was a prospective study in 58 paediatric patients (7.7 yrs. mean age) between 2000 and 2020 with aqueductal stenosis (11/58), obstruction of the aqueduct due to tumor growth (22/58),and connatal hydrocephalus (9/58). The average follow-up interval was 4.7 years. Head circumferences, Evans- and fronto-occipital horn ratios before and 3 months after ETV were obtained as Delta-indices. Furthermore ETV success score (ETVSS), the patency of the aqueduct pre- and postoperatively as well as of the stoma were assessed by flow void signs on MRI. Evaluation on MRI also included the shape of the floor of the 3^rd ventricle and whether or not the septum pellucidum showed signs of perforation. Four patients were analysed pre- and postoperatively via real-time MRI. At least the educational status regarding protected or unprotected education was analyzed. Results:The prevalence of a bowing of the floor of the 3^rd ventricle was 72%, and the ETVSS was 71.0%. In 26 children a septal perforations or an open aqueduct prior to ETV (19) could be identified. Mean ER and FOHR were reduced by 0.03 and 0.05 , respectively. Maintained open (flow void on postop MRI) or perforation could successfully be carried out during endoscopic surgery in 44 patients (79%). The disproportionate increase of head circumference abated in 79.4% of patients. New shunt insertion occurred in 16 patients (27.5%). Intraoperatively upward CSF flow was detected in all cases. Statistical analyses(ANOVA) showed significant results for unprotected education, postoperative ER and FOHR but not for open stoma. Conclusion: The identification of flow through the stoma on postoperative MRI seems to be a necessary but not sufficient condition for ETV success. In our study, ventricular volumes were used as parameters to determine success rates as well as unprotected education. Furthermore, enabling upward CSF flow driven by inspiration seems crucial for successful ETV.

Performing predictive maintenance (PdM) is challenging for many reasons. Dealing with large datasets which may not contain run-to-failure data (R2F) complicates PdM even more. When no R2F data are available, identifying condition indicators (CIs), estimating the health index (HI), and thereafter, calculating a degradation model for predicting the remaining useful lifetime (RUL) are merely impossible using supervised learning. In this paper, a 3 dof delta robot used for pick and place task is studied. In the proposed method, autoencoders (AEs) are used to predict when maintenance is required based on the signal sequence distribution and anomaly detection, which is vital when no R2F data is available. Due to the sequential nature of the data, non-linearity of the system, and correlations between parameter time series, convolutional layers are used for feature extraction. Thereafter, a sigmoid function is used to predict the probability of having an anomaly given CIs acquired from AEs. This function can be manually tuned given the sensitivity of the system or optimized by solving a minimax problem. Moreover, the proposed architecture can be used for fault localization for the specified system. Additionally, the proposed method is capable of calculating RUL using Gaussian process (GP), as a degradation model, given HI values as its input.

Diversity as well as temporal and spatial changes of the proportional abundances of different antibiotics (cycling, mixing or combinations thereof) have been hypothesised to be an effective administrative control strategy in hospitals to reduce the prevalence of antibiotic-resistant pathogens in nosocomial or community-acquired infections. However, a rigorous assessment of the efficacy of these control strategies is lacking. The main purpose here is to present a mathematical framework for the assessment of control stategies from a processual stance. To this end, we adopt diverse measures of heterogeneity and diversity of proportional abundances based on the concept of entropy from other fields and adapt them to the needs in assessing the impact of variations in antibiotic consumption on antibiotic resistance. Thereby, we derive a family of diversity measures whose members exhibit different degrees of complexity. Most important, we extent these measures such that they account for the assessment of temporal changes in heterogeneity including otherwise undetected diversity-invariant permutations of antibiotics consumption and prevalence of resistant pathogens. We apply a correlation analysis for the assessment of associations between changes of heterogeneities on the antibiotics and on the pathogen side. As a showcase, which serves as a proof-of-principle, we apply the derived methods to records of antibiotic consumption and prevalence of antibiotic-resistant germs from University Hospital Dresden. Besides the quantification of heterogeneities of antibiotics consumption and antibiotic resistance, we show that a reduction of prevalence of antibiotic-resistant germs correlates with a temporal change of similarity with respect to the first observation of antibiotics consumption, although heterogeneity remains approximately constant. Although an interventional study is pending, our mathematical framework turns out to be a viable concept for the assessment and optimisation of control strategies intended to reduce antibiotic resistance.

Lithium-ion batteries with improved energy densities have made understanding the Solid Electrolyte Interphase (SEI) generation mechanisms that cause mechanical, thermal, and chemical failures more complicated. SEI processes reduce battery capacity and power. Thus, a review of this area's understanding is important. It is essential to know how batteries degrade in EVs to estimate battery lifespan as it goes, predict, and minimize losses, and determine the ideal time for a replacement. Lithium-ion batteries used in EVs mainly suffer two types of degradation: calendar degradation and cycling degradation. Despite the existence of several existing works in the literature, several aspects of battery degradation remain unclear or have not been analyzed in detail. This work presents a systematic review of existing works in the literature. The results of the present investigation provide insight into the complex relationships among various factors affecting battery degradation mechanisms. Specifically, this systematic review examined the effects of time, side reactions, temperature fluctuations, high charge/discharge rates, depth of discharge, mechanical stress, thermal stress, and the voltage relationship on battery performance and longevity. The results revealed that these factors interact in complex ways to influence the degradation mechanisms of batteries. For example, high charge currents and deep discharges were found to accelerate degradation, while low temperatures and moderate discharge depths were shown to be beneficial for battery longevity. Additionally, the results showed that the relationship between cell voltage and State-of-Charge (SOC) plays a critical role in determining the rate of degradation. Overall, these findings have important implications for the design and operation of battery systems, as they highlight the need to carefully manage a range of factors to maximize battery performance and longevity. The result is an analysis of the main articles published in this field in recent years. This work aims to present new knowledge about fault detection, diagnosis, and management of lithium-ion batteries based on battery degradation concepts. The new knowledge is presented and discussed in a structured and comprehensive way.

In the semi-arid region of Brazil, it is common to use saline or brackish water for crop production. However, this practice can negatively affect the soil, nutrient balance, and fruit quality and production. From this perspective, this study aimed to evaluate the effect of fertilization combinations with nitrogen (N), phosphorus (P), and potassium (K) on the production and quality of West Indian cherry grown under salt stress in the second year of production. The study was conducted in a protected environment following a randomized block design with treatments distributed in a 2 x 10 factorial arrangement referring to two levels of electrical conductivity of irrigation water (ECw) (0.6 and 4.0 dS m-1) and 10 NPK fertilization combinations (80-100-100; 100-100-100; 120-100-100; 140-100-100; 100-80-100; 100-120-100; 100-140-100; 100-100-80; 100-100-120 e 100-100-140% of the recommendation in the second year of production), with three replicates and one plant per lysimeter. The results indicate that irrigation of West Indian cherry crop irrigation at the water salinity of 4.0 dS m-1 negatively affected all fruit production variables. The interaction between the ECw of 0.6 dS m-1 and the 100-80-120 NPK fertilization combination increased the total number of fruits and the total fruit weight of West Indian cherry.

Background: Vaccinating children against COVID-19 is an essential public health strategy in order to reach herd immunity and prevent illness among children and adults. Parents are facing tremendous stress in relation to the COVID-19 pandemic and the effectiveness of the COVID-19 vaccination program for children. In this study, we aimed to investigate parents’ willingness to vaccinate their children against COVID-19 in North Kivu province (DRC). Methods: A cross-sectional survey between December 01, 2021 to January 20, 2022 in 6 health zones (Goma, Karisimbi, Butembo, Beni, Kamango and Katwa) was conducted in the province of North Kivu. In each health zone, we selected 5 clusters (Health area) using the method of probabilistic selection proportional to population size. In total, 522 parents participated in our study. Results: Overall, 32.8% of parents intended to vaccinate their children. In the multivariate analysis, younger age of parents (aOR : 2.40, CI : [1.50-3.83]), higher level of fear that “a member of my family” could contract COVID-19 (aOR : 2.35, CI : [1.38-4.02]), higher level of perceived vulnerability to COVID-19 within the family (aOR : 1.70, CI : [1.005-2.2881]), higher level of perceived susceptibility to COVID-19 within the family (aOR : 3.07, CI : [1.80-5.23]), and history of vaccination against COVID-19 among parents (aOR : 16.47, CI : [8.39-32.33]), were significantly associated with the intention to have their children or adolescents vaccinated. Conclusion: Willingness of parents to vaccinate their children against the COVID-19 vaccination was low in North Kivu. There is undeniably in this region a need to reinsure the populations about vaccine safety for both children and adults. Public health authorities should also address widespread misinformation about vaccines in a timely manner.

The fourth Industrial Revolution, well-known as “Industry 4.0”, based on the integration of information and communication technologies, has introduced significant improvements in manufacturing. However, vision systems still experience various impracticalities in dealing with the effect of complex lighting on the systems platform. Therefore, a machine vision system for automatic identification of pen parts under varying lighting conditions at a digital learning factory is proposed. The developed vision system presents a straightforward approach by effectively minimizing the environmental lighting effect on the identification process. First, the obtained information of the designed vision framework is exported to a program, where a reduction of non-uniform illumination is achieved through the implementation of Retinex image enhancement techniques. Then, the color-based Fuzzy C-means (FCM) algorithm, including improved mark watershed segmentation, is employed for pen parts object classification. Finally, the position features of the selected pen part are reported. The process applied to a total number of 210 upper pen parts (caps) and 241 lower pen parts (tubes) images under different lighting scenarios. Results indicate that average parts identification precision for cap and tube parts is different and equals to 98.64% and 95.26%, respectively. The present methodology provides a promising scheme that can be feasibly adapted for other industrial Color-based object recognition applications.

With the emergence of COVID-19 we are confronted with a new clinical picture of acute respiratory distress syndrome in the intensive care unit. In the majority of patients, the respiratory mechanics are very different from the “normal” ARDS patient. We measured transpulmonary pressure and dead space ventilation to assess the effects of high and low PEEP levels on lung compliance and ventilation-perfusion mismatching. Advanced respiratory mechanics were assessed in 14 patients. Compared to ARDS patients, lung compliance was relatively high (61 ± 5 mL/cmH₂O). COVID-19 patients had high dead space ventilation and gas exchange impairment (Bohr 52 ± 3%; Enghoff modification 67 ± 2%; ventilatory ratio 2.24 ± 0.23). we show that higher PEEP levels decrease lung compliance and in most cases increase dead space ventilation, indicating that high PEEP levels probably cause hyperinflation in patients with COVID-19. We suggest using prone position for an extended period of time, and apply lower PEEP levels as much as possible.

The global increase in obesity has significant health implications, with an increased BMI as a known risk factor for diseases such as type 2 diabetes, cardiovascular diseases, or different cancer types. Long-term effectiveness of diet therapy in addressing morbid obesity is extremely limited with no adequate pharmaceutical agents available as treatment option resulting in bariatric surgery as being the only viable option to achieve and maintain significant long-term weight loss. One important role in the overall human health plays the gut microbiome and its complex composition, which is usually altered and reduced in complexity/diversity in severely obese patients. In this study, the influence of bariatric surgery and the resulting weight-loss on the gut microbiome composition of twelve morbid obese (BMI ≥ 40) female adult central European patients was investigated by comparing the relative abundances of the major microbial phyla Actinobacteria, Bacteroidetes, Firmicutes, Proteobacteria prior- and post-surgery. We also aimed to give insight into the major changes of individual prominent and promising future probiotic bacteria characterized by an overall increase in abundance accompanied by a switch of enterotypes. Identifying specific microbial alterations associated with successful weight-loss outcomes may contribute to the development of future therapeutic interventions by supplementation with next-generation probiotics.

Our previous research provides evidence that vergence eye movements may significantly influence cognitive processing and could serve as a reliable measure of cognitive issues. The rise of consumer-grade eye tracking technology, which uses sophisticated imaging techniques in the visible light spectrum to determine gaze position, is noteworthy. In our study, we explored the feasibility of using webcam-based eye tracking to monitor the vergence eye movements of patients with Mild Cognitive Impairment (MCI) during a visual oddball paradigm. We simultaneously recorded eye positions using a remote infrared-based pupil eye tracker. Both tracking methods demonstrated more pronounced cognitive vergence responses for targets as opposed to distractors. In summary, the use of a consumer-grade webcam to record cognitive vergence shows potential. This method could potentially lay the groundwork for future research aimed at creating an affordable screening tool for mental health care.

Social networks are experiencing great popularity, with Instagram currently being the most intensively used network. On these platforms, users are continuously exposed to self-relevant information that fosters social comparisons. A distinction is made between ability-based and opinion-based comparison dimensions. To experimentally investigate the influence of these comparison dimensions on users' subjective well-being, an online exposition experiment (N = 409) was conducted. In a preliminary study (N = 107), adequate exposition stimulus material was selected in advance. The results of the main study indicated that exposition of ability-related social comparisons in the context of social media elicited lower well-being than exposition of opinion-related social comparisons. Theoretical and practical implications of the findings were discussed and suggestions for future work were outlined.

To combat infections on biomedical devices, antimicrobial coatings have attracted considerable attention, including coatings comprising naturally occurring antimicrobial peptides (AMPs). In this study the aim was to explore performance upon extended challenge by bacteria growing in media above samples. The AMPs LL37, Magainin 2, and Parasin 1 were covalently grafted onto a plasma polymer platform, which enables application of this multilayer coating strategy to a wide range of biomaterials. Detailed surface analyses were performed to verify the intended outcomes of the coating sequence. Samples were challenged by incubation in bacterial growth media for 5 and 20 hrs. Compared with the control plasma polymer surface, all three grafted AMP coatings showed considerable reductions in bacterial colonization even at the high bacterial challenge of initial seeding at 1x107 CFU, but there were increasing numbers of dead bacteria attached to the surface. All three grafted AMP coatings were found to be non-toxic to primary fibroblasts. These coatings thus could be useful to produce antibacterial surface coatings for biomaterials, though possible consequences arising from the presence of dead bacteria need to be studied further, and compared to non-fouling coatings that avoid attached dead bacteria.

At the highest level of endurance sports, the differences in finishing times are small, so equipment is constantly being constantly improved to enhance the athletes' performance. For instance, one dominant resistive force in connection with cross-country skiing is the friction between the skis and snow and since the 1930s, research designed to understand and reduce this friction has been ongoing. The mechanisms involved in ski-snow friction include compaction, micro-ploughing, adhesion, viscosity, and water-bridging. Of these, adhesive and viscous friction have been most studied, while much less is presently known about compaction, micro-ploughing, and water-bridging. At the macro-scale, the ski-camber profile plays a key role in determining whether, with respect to friction, a particular cross-country ski is suitable for use under a given set of conditions. Through its influence on where ski-snow contact occurs, this ski-camber profile has a profound impact on adhesive and viscous friction, micro-ploughing, the formation of water bridges, and the rate of compaction. Different contact zones with different apparent areas of contact and pressure have been found to be most suitable for different conditions. In addition, the micro-scale texture of the ski base is also an important determinant of ski-snow friction. Topographical measurements of this texture can be achieved with white-light interferometer and recent characterisation has focused on the mechanical properties of contact. In numerous tribological studies the interactions between features at different scales are modelled. In most tribological systems, features on several scales influence friction and ski-snow contact is certainly no exception. Accordingly, the current investigation was designed to evaluate the multi-scale properties of different combinations of two skis with two different base textures. The real area of contact and the average interfacial separation and total average reciprocal interfacial separation between the ski and snow were taken into consideration. We found that different macro- and micro-scale properties of the ski favour different mechanisms of friction. Both the profile of the ski camber and texture of the base play decisive roles in determining viscous friction. At the same time, the texture of the ski base exerts a greater impact on the average real contact pressure, real contact area and minimal average interfacial separation between the ski and snow than does the ski-camber profile.

This paper summaries the main findings from the full-scale CFD analyses conducted at SINTEF Ocean on the case of MV REGAL, which is one of the benchmark vessels studied in the ongoing joint industry project JoRes. The numerical approach is described in detail, and comparative results are presented regarding the propeller open water characteristics, ship towing resistance, and ship self-propulsion performance. The focus of numerical investigations is on the assessment of the existing simulation best practices applied to a ship scale case in a blind simulation exercise, and performance of thereof with different turbulence modelling methods. The results are compared directly with full-scale performance predictions based on model tests conducted at SINTEF Ocean and sea trails data obtained in the JoRes project.

Recent empirical work has revealed that drivers have different lane change strategies. These strategies help to understand driver heterogeneity and decision stochasticity, which are both often lacking in microscopic models. In this paper we generalize the lane change strategies in a theory for social interactions. The theory introduces a mechanism by which two new driver traits, ego-speed sensitivity and socio-speed sensitivity, endogenously influence other driver traits that govern lane change behaviour such as desired speed, desired headway and lane change desire. A key concept in this mechanism is that drivers are not just affected by what happens in front of them, but also by what they observe in their rear-view mirrors. The idea is that drivers reduce their headways to exert (social) pressure onto leading drivers (on the same or adjacent lanes), which may force them to increase speed, change lanes, or conversely, to refrain from changing lanes. We refer to this reduction of the headway as tailgating. Through an example implementation of the theory, we demonstrate that these social interactions may have a profound impact on several key (mesoscopic) traffic flow characteristics. Our results show that these new driver interactions influence the number of lane changes, platoon lengths, and headway variance. As such, the theory improves our description and understanding of traffic flow and consequently it paves the path for more realistic traffic models.

Socioeconomic conditions and social attitudes are known to represent epidemiological determinants. Credible knowledge on socioeconomic driving factors of the COVID-19 epidemic is still incomplete. Based on a linear random effects regression, a predictive model is derived to estimate COVID-19 incidence in German rural districts from local socioeconomic factors and popularity of political parties in terms of their share of vote. Thereby, time series provided by Germany's public health institute (Robert Koch Institute) of weekly notified 7-day incidences per 100,000 inhabitants per district from the outset of the epidemic in 2020 up to December 1, 2021, have been used to construct the dependent variable. Local socioeconomic conditions including share of votes, retrieved from the Federal Statistical Office of Germany, have been used as potential risk factors. Popularity of the right-wing party Alternative for Germany (AfD) bears a considerable risk of increasing COVID-19 incidence both in terms of predicting the maximum incidences during three epidemic periods (alternatively, cumulative incidences over the periods are used to quantify the dependent variable) and in a time-continuous sense. Thus, districts with high AfD popularity rank on top in the time-average regarding COVID-19 incidence. The impact of the popularity of the Free Democrats (FDP) is markedly intermittent in the course of time showing two pronounced peaks in incidence but also occasional drops. A moderate risk emanates from popularities of the Green Party (GRÜNE) and the Christian Democratic Union (CDU/CSU) compared to the other parties with lowest risk level. Socioeconomic parameters like \emph{per capita} income, proportions of protection seekers and social benefit claimants, and educational level have negligible impact. To the contrary, incidence significantly increases with population density. In order to effectively combat the COVID-19 epidemic, public health policymakers are well advised to account for social attitudes and behavioural patterns reflected in local popularities of political parties, which are conceived as proper surrogates for these attitudes. Whilst causal relations between social attitudes and the presence of parties remain obscure, the political landscape in terms of share of votes constitutes at least viable predictive "markers" relevant for public health policy making.

While lidar-based forest inventory methods have been widely demonstrated, prediction of tree diameters with lidar is not well understood. The performance metrics typically used in studies for prediction of diameters can be difficult to interpret and may not support comparative inferences between sampling designs or study areas. We evaluate a variety of lidar and k nearest neighbor (k-NN) strategies for prediction of tree diameter distributions using two indices which are easier to interpret and compare. The indices are based on the coefficient of determination (R²), and root mean square deviation (RMSD). These indices facilitate comparisons with alternative (non-lidar) inventory strategies, and with other project areas. We evaluate k nearest neighbors (k-NN) dbh density (relative frequency by dbh class) prediction strategies with lidar for 190 training plots distribute across the 800 km² Savannah River Site in South Carolina, USA. We evaluate the performance of k-NN with respect to distance metrics, number of neighbors, predictor sets, and response sets. Amongst the examined strategies we found Mahalanobis distance with k = 3 neighbors performed best according to a number of criteria.

As the EU is moving towards a low carbon economy and seeks to further develop its renewable energy policy, this paper quantitatively investigates the impact of plausible energy market reforms from the perspective of bio-renewables. Employing a state-of-the-art biobased variant of a computable general equilibrium model, this study assesses the perceived medium-term benefits, risks and trade-offs which arise from an advanced biofuels plan, two exploratory scenarios of a more 'sustainable' conventional biofuels plan and a 'no-mandate' scenario. Consistent with more recent studies, none of the scenarios considered present significant challenges to EU food-security or agricultural land usage. An illustrative advanced biofuels plan simulation requires non-trivial public support to implement whilst a degree of competition for biomass with (high-value) advanced biomass material industries is observed. On the other hand, it significantly alleviates land use pressures, whilst lignocellulose biomass prices are not expected to increase to unsustainable levels. Clearly, these observations are subject to assumptions on technological change, sustainable biomass limits, expected trends in fossil fuel prices and EU access to third-country trade. With these same caveats in mind, the switch to increased bioethanol production does not result in significant market tensions in biomass markets.

Indonesia's government anticipates waste problems by managing them through a large number of waste reduction programs. From a governance perspective in Indonesia, it is known that actors from diverse governmental levels and across sectors are involved in waste management, and their involvement largely depends on their institutional goals and problems. Hence, they are expected to coherently collaborate together by developing and implementing sustainable instruments and resources for improving waste management problems. However, it is necessary to understand how supportive and restrictive the governance of waste reduction programs is to encourage successful trash reduction. This study is designed to evaluate and examine the application of Community-Based Solid Waste Management (CBSWM) in Makassar. In this research, The Governance Assessment Tool (GAT) was applied to analyze the governance context of the waste reduction programs in Makassar qualitatively. From the assessment, contexts can be described as either supportive or restrictive of the processes of implementing public policies on waste management. As a result of such an assessment, this study shed light on some opportunities to improve the governance of waste management implementation's impact on reducing waste in Makassar, South Sulawesi, Indonesia. The conclusion of this study depicts that the most important actors are affiliated with the local government and the community. Moreover, this study shows that the assessment of contextual governance is predominantly restrictive.

Transient liquid phase (TLP) bonding of Al-6063 and UNS S32304 was performed using copper foil as an interlayer between the base metals. A compression load was applied normal to the specimens. Metallurgical examination of the produced joints showed three distinct regions including a reaction zone, diffusion affected zone and the base metals. The diffusion of copper into aluminum resulted in an Al-Cu eutectic structure. However, the oxide layer on the aluminum surface controlled the dissolution behavior of copper and the extent of its wettability with the base metals. Although voids and intermetallic compounds were detected at the interfaces of the processed joints, a defect free joint was produced at 570°C. In addition, the results from corrosion tests showed that the use of copper as an interlayer decreased the corrosion resistance of the joints. However, increase in thickness of the joining reaction zone with increasing bonding temperature was observed to increase corrosion resistance.

This study presents the manufacturing process driven development of an interlocking metasurface mechanism (ILM) for Fused Filament Fabrication (FFF) with a focus on open-source accessibility. The presented ILM is designed to enable strong contact between to planar surfaces. The mechanism consists of spring elements and locking pins which snap together when forced into contact. The mechanism is designed to optimize mechanical properties, functionality and printability with common FFF printers. The mechanisms is printed from thermoplastic polyurethane (TPU) filament which was selected for its flexibility, crucial for spring element performance and tolerances of the fabrication method. To characterize the designed mechanism a tensile test is carried out to assess the holding force of the ILM. The force-displacement profiles are analyzed and categorized into distinct phases, highlighting the interplay between spring deformation, sliding, and disengagement. The results show variations in holding forces attributed to geometric and material-related factors. The testing results are compared and discussed to a numerical simulation carried out with a frictionless approach with a nonlinear Neo–Hookean material law. The study underscores the importance of meticulous parameter control in 3D printing for consistent and reliable performance of interlocking metasurface mechanisms. The investigation leads to a scalable model of a ILM element pair with a distinct three-phase snapping characteristics ensuring reliable holding capabilities.

Abstract: Metal-air batteries provide a most promising battery technology given their outstanding potential energy densities, which are desirable for both stationary and mobile applications in a ‘beyond lithium-ion’ battery market. Silicon- and iron-air batteries underwent less research and development compared to lithium- and zinc-air batteries. Nevertheless, in the recent past, the two also-ran battery systems made considerable progress and attracted rising research interest due to the excellent resource-efficiency of silicon and iron. Silicon and iron are among the top five of the most abundant elements in the earth’s crust, which ensures almost infinite material supply of the anode materials, even for large scale applications. Furthermore, primary silicon-air batteries are set to provide one of the highest energy densities among all batteries, while iron-air batteries are frequently considered as a highly rechargeable system with decent performance characteristics. Considering fundamental aspects for the anode materials, i.e., the metal electrodes, in this review, we will first outline the challenges, which explicitly apply to silicon- and iron-air batteries and prevented them from a broad implementation so far. Afterwards, we provide an extensive literature survey regarding state-of-the-art experimental approaches, which are set to resolve the aforementioned challenges and might enable the introduction of silicon- and iron-air batteries into the battery market in the future.

It is well known that low back pain (LBP) prevalence is high during the course of school age children’s lives. However, literature concerning the initial onset of back pain between ages of 3 and 11 years remains scarce. The present study aimed to analyze the prevalence of LBP in kindergarten and primary school students. 278 (9.9±2.1 years old; 52.2% girls) students from two public kindergarten and primary schools in Valencia, Spain participated in this cross-sectional study. The Nordic questionnaire on LBP was used to ask questions related to the duration of LBP symptoms over time. The lifetime prevalence of LBP was 47.5% (n = 132), a last year prevalence of 44.2% (n = 123), and a last week prevalence of 18.8% (n = 50) was reported. Boys and girls reached lifetime prevalence of 52.3% (n = 64) and 47.7% (n = 82) (χ2 = 1.978, p = .099), respectively. By age group, lifetime episodes of LBP also showed a higher prevalence with increasing age (χ2 = 32.637; p &lt; .001). In summary, our findings suggest that LBP increases with age. In addition, our results further strengthen the evidence that LBP onset could start as young as 10-years-old.

Digital enabled manufacturing systems require high level of automation for fast and low-cost production but should also present flexibility and adaptiveness to varying and dynamic conditions in their environment, including the presence of human beings; However, this presence of workers in the shared workspace with robots decreases the productivity as the robot is not aware about the human position and intention which leads to concerns about the human safety. This issue is addressed in this work by designing a reliable safety monitoring system for collaborative robots (Cobots). The main idea here is, to significantly enhance safety by a combination of recognition of human actions using visual perception and at the same time interpreting physical human-robot contact by tactile perception. Two datasets containing contact and vision data are collected by using different volunteers. The action recognition system classifies human actions using the skeleton representation of the latter when entering the shared workspace and the contact detection system distinguishes between intentional and incidental interactions if a physical contact between human and cobot takes place. Two different deep learning networks are used for human action recognition and contact detection which in combination, are expected to lead to the enhancement of human safety and an increase of the level of cobot perception about human intentions. The results show a promising path for future AI-driven solutions in safe and productive human–robot collaboration (HRC) in industrial automation.

The COVID-19 pandemic is one of the largest challenges in medicine and health care worldwide in recent decades, and it is infecting and killing increasing numbers of people every day. In this paper, we discuss the possible relationships among lysosomotropism, increasing lysosomal pH, and the SARS-CoV-2 infection and disease process, and we deduce a possible approach for treatment and prophylaxis. Lysosomotropism is a biological characteristic of small molecules, such as (hydroxyl)chloroquine, amitriptyline, NB 06, or sertraline, which is present in addition to intrinsic receptor-mediated or enzymatic pharmacological effects. Lysosomotropic compounds affect prominent inflammatory messengers, such as IL1B, CCL4, CCL20, and IL6, as well as cathepsin L dependent viral entry (fusion) into host cells. Therefore, this heterogeneous group of compounds is a promising candidate for the prevention and treatment of SARS-CoV-2 infections, as well as influenza A infections and cytokine release syndrome (CRS) triggered by bacterial or viral infections. Patients who have already taken medications with lysosomotropic compounds for other pre-existing conditions may benefit from this treatment in the COVID-19 pandemic. Increased lysosomal pH levels play an important role in the disease process in common skin disorders, such as psoriasis and atopic dermatitis, thus suggesting that affected individuals might benefit from their particular conditions in the COVID-19 pandemic. We suggest data analysis of patients with these diseases, and who are treated with lysosomotropic compounds, and, if the results are promising, subsequent clinical testing of off-label therapy with clinically approved lysosomotropic compounds in the current COVID-19 pandemic and future influenza A pandemics.

Abstract: Background: Intensity modulated radiotherapy (IMRT) is still a standard of care for radiotherapy in locally advanced head and neck cancer (LA-HNSCC). Simultaneous integrated boost (SIB) and moderate hypofractionation offer an opportunity for individual dose painting and a reduction in overall treatment time. We present retrospective data on toxicity and locore-gional control of a patient cohort with LA-HNSCC treated with an IMRT-SIB concept in compar-ison to normofractionated 3D-conformal radiotherapy (3D-RT) after a long-term follow-up. Methods: Between 2012 and 2014, n=67 patients with HNSCC (stages III/IV without distant me-tastases) were treated with IMRT-SIB either definitively (single/total doses: 2.2/66 Gy, 2.08/62.4 Gy, 1.8/54 Gy in 30 fractions) or in the postoperative setting (2.08/62.4 Gy, 1.92/57.6 Gy, 1.8/54 Gy). These patients' clinical courses were matched (for sex, primary, and treatment concept) as part of a matched-pair analysis with patients treated before mid-2012 with normofractionated 3D-CRT (definitive: 2/50 Gy followed by a sequential boost up to 70 Gy; postoperative: 2/60-64 Gy). Chemotherapy/ immunotherapy was given concomitantly in both groups in the definitive situation (postoperative dependent on risk factors). The primary endpoints were acute and late toxicity; the secondary endpoint was locoregional control (LRC). Results: Sixty-seven patients treated with IMRT-SIB (n = 20 definitive, n = 47 adjuvant) were matched with 67 patients treated with 3D-RT. There were minor imbalances between the groups concerning nonmatching variables such as extracapsular extension (ECE) and chemotherapy in IMRT-SIB. Significantly less toxicity was found in favor of IMRT-SIB concerning dysphagia, ra-diation dermatitis, xerostomia, fibrosis, and lymphedema. After a median follow-up of 63 months, the median LRC was not reached (IMRT-SIB) vs. 69.5 months (3D-RT) (p=0.63). Conclusions: This moderately hypofractionated IMRT-SIB concept was shown to be feasible with less toxicity than conventional 3D-RT in this long-term follow-up observation.

Battery electric vehicles provide an opportunity to balance supply and demand in future power systems with high shares of fluctuating renewable energy. Compared to other storage systems such as pumped-storage hydroelectricity, electric vehicle energy demand is highly dependent on charging and connection choices of vehicle users. We present a model framework of a utility-based stock and flow model, a utility-based microsimulation of charging decisions, and an energy system model including respective interfaces to assess how the representation of battery electric vehicle charging affects energy system optimization results. We then apply the framework to a scenario study for controlled charging of nine million electric vehicles in Germany in 2030. Assuming a respective fleet power demand of 27 TWh, we analyze the difference between power-system-based and vehicle user-based charging decisions in two respective scenarios. Our results show that taking into account vehicle users’ charging and connection decisions significantly decreases the load shifting potential of controlled charging. The analysis of marginal values of equations and variables of the optimization problem yields valuable insights on the importance of specific constraints and optimization variables. In particular, state-of-charge assumptions and representing fast charging drive curtailment of renewable energy feed-in and required gas power plant flexibility. A detailed representation of fleet charge connection is less important. Peak load can be significantly reduced by 5% and 3% in both scenarios, respectively. Shifted load is very robust across sensitivity analyses while other model results such as curtailment are more sensitive to factors such as underlying data years. Analyzing the importance of increased BEV fleet battery availability for power systems with different weather and electricity demand characteristics should be further scrutinized.

New experimental and clinical findings question the historic view of hydrocephalus and its 100-year-old classification. In particular, real-time MRI evaluation of CSF flow and detailed insights into brain water regulation on the molecular scale indicate the existence of at least three main mechanisms that determine the dynamics of neurofluids. (i) Inspiration is a major driving force (ii) Adequate filling of brain ventricles by balanced cerebrospinal fluid upsurge is sensed by cilia (iii) The perivascular glial network connects the ependymal surface to the pericapillary Virchow-Robin spaces. Hitherto, these aspects have not been considered a common physiologic framework improving knowledge and therapy for severe disorders of normal-pressure and post-haemorrhagic hydrocephalus, spontaneous intracranial hypotension and spaceflight disease.

Microbial electrochemical technologies (MET) rely on the presence of the metabolic activity of electroactive bacteria for the use of solid-state electrodes for oxidizing different kind of compound, that could lead to the synthesis of chemicals, bioremediation of polluted matrices, the treatment of contaminants of interest, as well as the recovery of energy. Keeping in mind those possibilities, since the beginning of the present century, there has been a growing interest in the use of electrochemical technologies for wastewater treatment, and if possible with simultaneous power generation. In the last years, there has been a growing interest to explore the possibility of merging MET with constructed wetlands, to offer a new option of intensified wetland system that could keep a high performance with a lower footprint. Based on that interest, this paper explains the general principles of MET, and the different known extracellular electron transfer mechanisms ruling the interaction between electroactive bacteria and potential solid-state electron acceptors. Also, the adoption of those principles for the development of MET set-ups for simultaneous wastewater treatment and power generation, and the challenges that the technology face. Ultimately, the most recent developments in set-ups that merges MET with constructed wetlands are presented and discussed.

Abstract Plant diseases are responsible for over 10% loss in global food production and have serious impacts on world-wide food security across several countries. Amongst these diseases, those caused by viroids are highly significant, accounting for extensive damage to crops every year and pose a major economic threat to agricultural crops. Combined infections with viroids, plant viruses and their satellites further exacerbate the situation. Vector transmission of viroids necessitates the use of pesticides, thus incurring high costs in addition to eliciting several detrimental effects on the ecosystem due to the noxious outcomes of pesticide use. The current review addresses the major economic impacts of viroids on crops, costs to the world economy and impacts on regions, farmers and consumers in addition to describing remediation measures to mitigate the losses caused by these subviral agents. Also described are issues relating to the pros and cons of pesticide use, the compelling need towards sustainable agricultrual practices while reducing pesticide use. In particular, the role of RNAi and genome editing technologies towards amelioration of agricultural loss is discussed.

Vitamin D is crucial for athletes' health and performance. Although the exact vitamin D requirements for athletes have not been established, maintaining 25(OH)D levels of at least 40 ng/ml is considered beneficial. This study aimed to determine whether an individual loading dose formula for vitamin D supplementation is suitable to meet a target value of 40 ng/ml and is more effective than standardized supplementation. In a 10-week supplementation study during the winter months in Germany, 90 athletes with insufficient vitamin D levels (25(OH)D<30ng/ml) were randomly assigned to receive either a universal dose of 2000 IU/day of vitamin D or a loading dose of 4000 IU/day, followed by a maintenance dose of 1000 IU/day. Total 25(OH)D concentration was measured from dried blood spots at three time points: at baseline, at the computed date of 40ng/ml, and after the 10-week period. Additionally, a vitamin D-specific questionnaire was issued. On the day when 25(OH)D blood concentrations of 40 ng/ml were calculated to prevail, the individualized group had a significantly higher 25(OH)D level than the standardized group (41.1+-10.9 ng/ml vs. 32.5+-6.4 ng/ml, p<0.001). This study demonstrated that the examined formula is suitable for athletes to achieve a 25(OH)D concentration of 40 ng/ml. This indicates that a personalized approach is more effective than a one-size-fits-all approach in restoring adequate vitamin D levels in athletes.

As the production of battery cells experiences exponential growth and electric vehicle fleets continue to expand, an escalating number of traction batteries are nearing the conclusion of their operational life for mobility purposes, both presently and in the foreseeable future. Concurrently, the heightened interest in sustainable energy storage solutions has spurred investigations into potential second-life applications for aging traction batteries. Nonetheless, the predominant practice remains the removal of these batteries from electric vehicles, signifying the end of their life cycle, and their subsequent incorporation into recycling processes, with limited consideration for life-extending measures. This study seeks to elucidate the reasons behind the deprioritization of battery repurposing strategies. Therefore, the research team conducted two industry studies with over 20 battery experts from Europe, revealing concerns about the economic viability of repurposing batteries for stationary storage applications. A literature review of studies published since 2016 confirmed the industry's struggles to address this issue theoretically. In conclusion, a research question was formulated, and a solution approach was delineated to assess the economic prospects of aged traction batteries within the industry's landscape in the future. This solution approach encompasses pertinent market analysis, the identification of representative second-life applications, as well as the formulation of a methodology for evaluating the residual value of these batteries.

Cytokines are mediators of inflammation that could lead to fibrosis. The aim was to monitor cytokine levels in saliva and serum after locally fractionated radiotherapy of the head and neck in mice and investigate associations with salivary gland fibrosis and hyposalivation. C57BL/6 mice were randomized to sham or X-ray irradiation of 66 Gy in 10 fractions over 5 days. Blood and saliva were collected on day -7, 5, 35, 80 and 105 with following cytokine analysis. The harvested submandibular salivary gland was assessed for presence of fibrosis. Decision tree regression analysis was used to investigate whether cytokine levels could predict late endpoints in terms of hyposalivation or fibrosis. Significant formation of fibrosis in gland tissue and reduced saliva production was found after irradiation. The pro-inflammatory cytokines IL-1α, TNF, TIMP1, G-CSF, KC and MIP-1α showed increased levels in saliva in irradiated mice and strong correlation with late endpoints. The decision tree analysis largely separated controls from irradiated animals with IL-1α being the strongest predictor. Pro-inflammatory cytokines in saliva, but not in serum, were associated with late endpoints. This indicates that cytokine expression in saliva is a good biomarker for local salivary gland damage with IL-1α as the strongest single predictor.

The α-synucleinopathies are a group of neurodegenerative diseases characterized by the deposition of α-synuclein aggregates (α-syn) in the brain. Currently, there is no suitable tracer to enable a definitive early diagnosis of these diseases. We reported candidates based on 4,4'-disarylbisthiazole (DABTA) scaffold with a high affinity towards α-syn and excellent selectivity over Aβ and tau fibrils. Based on prior in silico studies a focused library of 23 halide-containing and O-methylated DABTAs was prepared. The DABTAs were synthesized via a modified two-step Hantzsch thiazole synthesis, characterized, and used in competitive binding assays against [3H]PiB, and [3H]DCVJ. The DABTAs gave an overall chemical yield of 15 – 71%, with a calculated lipophilicity of 2.5 – 5.7. The ligands demonstrated an excellent affinity to α-syn with both [3H]PiB and [3H]DCVJ: Ki 0.1 – 4.9 nM and up to 20 – 3900-fold selectivity over Aβ and tau fibrils. It could be concluded that in-silico simulation is useful for the rational design of a new generation of DABTAs. Further investigation of the leads in the next step is encouraged: radiolabeling of the ligands with radioisotopes such as fluorine-18 or carbon-11 for in vivo, ex vivo and translational research and for further in vitro experiments on human-derived protein aggregates.

To further understand the role of phosphorylation in ISGF3- and STAT2/IRF9-mediated constitutive and long-term IFN-I-stimulated transcriptional responses, we performed RNA-Seq and ChIP-Seq, in combination with phosphorylation inhibition and anti-viral experiments. First, we identified a group of ISRE-containing ISGs that were commonly regulated in IFNα treated WT and STAT1-KO cells. Thus, in 2fTGH and Huh7.5 WT cells IFNα-inducible transcription and anti-viral activity relied on the recruitment of the ISGF3 components STAT1, STAT2 and IRF9 in a phosphorylation- and time-dependent manner. Likewise, in ST2-U3C and Huh-STAT1KO cells lacking STAT1, ISG expression correlated with DNA-binding of phosphorylated STAT2/IRF9. This pointed to a dominant role of classical ISGF3 and STAT2/IRF9, and not U-ISGF3 or U-STAT2/IRF9, in the regulation of early and prolonged ISG expression and viral protection, in WT and STAT1-KO cells. In addition, comparative experiments in U3C (STAT1-KO) cells overexpressing all ISGF3 components (ST1-ST2-IRF9-U3C), revealed a threshold-dependent role of U-ISFG3, and potentially U-STAT2/IRF9, in the regulation of constitutive and possibly long-term IFNα-treated ISG expression and anti-viral activity.

Intracranial metastases from thyroid cancer are rare. Although the prognosis of thyroid cancer patients is generally favorable, the prognosis of patients with intracranial metastases from thyroid cancer has been considered unfavorable having a lower survival rate than those without intracranial involvement. Many questions about their management remain unclear. The aim of this study was to analyze the characteristics, treatments, and outcomes of patients with brain metastases from thyroid cancer. Among 4320 patients with thyroid cancer recorded in our institutional database over a 30-year period, 20 patients with brain metastasis were retrospectively collected and analyzed. The clinical characteristics, histological type of primary cancer and metastatic brain tumor, additional previous distant metastasis, treatment modalities, locations and characteristics on radiologic findings, time interval between the first diagnosis of the primary thyroid cancer and brain metastasis, and survival were analyzed. The mean age at initial diagnosis was 59.3 ± 14.1 years, and at the manifestation of diagnosis of cerebral metastasis 64.8 ± 14.9 years. The histological types of the primary thyroid cancers were papillary in ten patients, follicular in seven, and poorly differentiated carcinoma in three. The average interval between the diagnosis of thyroid cancer and brain metastasis was 63.4 ± 58.4 months (range, 0-180 months). Ten patients had a single intracranial lesion and 10 patients had multiple lesions. Surgical resection was primarily performed in 15 patients and whole-brain radiotherapy, radiotherapy or tyrosine kinase inhibitors were applied in the other 5 patients. Overall median survival time was 15 months after diagnosis of BM from TC (range: 1-252 months). Patients with thyroid cancer can develop brain metastasis even many years after diagnosis of the primary tumor. Our study demonstrates an increased overall survival of patients younger than 60 years of age at the time of diagnosis of brain metastasis. There was no difference in survival between patients with brain metastasis from papillary or follicular thyroid carcinoma.

In winter sports, the equipment often comes into contact with snow or ice, and this contact generates a force that resists motion. In some sports, such as cross-country skiing, this resistive force can significantly affect the outcome of a race, as a small reduction in this force can give an athlete an advantage. Researchers have examined the contact between skis and snow in detail, and to fully understand this friction, the entire ski must be studied at various scales. At the macro scale, the entire geometry of the ski is considered and the apparent contact between the ski and the snow is considered and at the micro scale the contact between the snow and the ski base ski-base textures. In the present work, a method for characterising contact between the ski-base texture and virtual snow will be presented. Six different ski-base textures will be considered. Five of them are stone-ground ski bases, and three of them have linear longitudinal textures with a varying number of lines and peak-to-valley height, and the other two are factory-ground “universal” ski bases. The sixth ski base has been fabricated by a steel-scraping procedure. In general, the results show that a ski base texture with a higher Spk-value has less real contact area, and that the mutual differences can be large for surfaces with similar Sa-values. The average interfacial separation is, in general, correlated with the Sa-value, where a “rougher” surface exhibits a larger average interfacial separation. The results for the reciprocal average interfacial separation, which is related to the Couette type of viscous friction, were in line with the general consensus that a “rougher” texture performs better at high speed than a “smoother” one, and it was found that a texture with high Sa and Spk values resulted in a low reciprocal average interfacial separation and consequently low viscous friction. The reciprocal average interfacial separation was found to increase with increasing real contact area, indicating a correlation between the real area of contact and the Couette part of viscous friction.

Sustainable Development Goal (SDG) 6.2 sets an ambitious target of leaving no one without adequate sanitation by 2030. The key concern is the lack of local human and financial capital to fund the collection of reliable information to monitor progress towards the goal. As a result, national and local records may be telling a different story of the proportion of safely managed sanitation that counts towards achieving the SDGs. This paper unveils such inconsistency in sanitation data generated by urban authorities and proposes a simple approach for collecting reliable and verifiable information on access to safely managed sanitation. The paper is based on a study conducted in Babati Town Council in Tanzania. Using a smartphone-based survey tool, city health officers were trained to map 17,383 housing units in the town. A housing unit may comprise of two or more households. The findings show that 5% practice open defecation, while 82% of the housing units have some forms of sanitation. Despite the extensive coverage, only 31% of the faecal sludge generated is safely contained, while 64% is not. This study demonstrates the possibility of using simple survey tools to collect reliable data for monitoring progress towards safely managed sanitation in the towns of global south.

Among the thermophysical properties, the surface / interfacial tension, viscosity and density / molar volume of liquid alloys are the key properties for the modelling of microstructural evolution during solidification. Therefore, only reliable input data can yield accurate predictions preventing the error propagation in numerical simulations of solidification related processes. Due to experimental difficulties related to reactivity of metallic melts at high temperatures, the measured data are often unreliable or even lacking. The application of containerless processing techniques either leads to a significant improvement of the accuracy or makes the measurement possible at all. On the other side, accurate model predicted property values could be used to compensate the missing data; otherwise, the experimental data are useful for the validation of theoretical models. The choice of models is particularly important for the surface, transport and structural properties of liquid alloys representing the two limiting cases of mixing, i.e. ordered and phase separating alloy systems. To this aim, the thermophysical properties of the Fe-Si and Cu-Pb systems were analysed and the connections with the peculiarities of their mixing behaviours are highlighted.

After UV excitation, gas phase thymine returns to ground state in 5 to 7 ps, showing multiple time constants. There is no consensus on the assignment of these processes, with a dispute between models claiming that thymine is trapped either in the first (S1) or in the second (S2) excited states. In the present study, nonadiabatic dynamics simulation of thymine is performed on the basis of ADC(2) surfaces, to understand the role of dynamic electron correlation on the deactivation pathways. The results show that trapping in S2 is strongly reduced in comparison to previous simulations considering only non-dynamic electron correlation on CASSCF surfaces. The reason for the difference is traced back to the energetic cost for formation of a CO p bond in S2.

Positive Health (PH) has been described as a promising transformative innovation to address the challenges of promoting well-being and reducing the burden of disease. The aim of this study is to review the current state of knowledge about PH as introduced by Huber et al. (2016) within the available scientific literature. A rapid review of the literature following the Cochrane Rapid Review recommendations. Three databases were searched (PubMed, Google Scholar, and CINAHL). Data were extracted and synthesized using a narrative approach. A total of 55 articles were included. Initial evaluation studies reveal promising results both at individual and collective levels. However, a need is expressed in several articles for further refinement of the conceptualization of PH and ways to make the effects of the PH approach more measurable. Professionals also expressed a desire for a more informed application and elaboration of the PH method across various settings and populations to enhance its effectiveness in practice. This rapid review highlights the transformative potential of PH in shifting from a disease-focused to a health-oriented paradigm of healthcare. It underscores the need for continued research regarding further development of the concept and its practical method, along with the necessity for methodological innovation.

The concept of {\it quantum ratio} emerged in the recent efforts to understand how Newton's equations appear for the center of mass (CM) of an isolated macroscopic body at finite body-temperatures, as the first approximation to quantum-mechanical equations. It is defined as $Q\equiv R_q/L_0$, where the quantum fluctuation range $R_q$ is the spatial extension of the pure-state CM wave function, whereas $L_0$ stands for the body's linear size (the space support of the internal, bound-state wave function). The two cases $R_q /L_0 \lesssim 1$ or $R_q/ L_0 \gg 1$, roughly correspond to the body's CM behaving classically or quantum mechanically, respectively. In the present note we elaborate more on this concept, illustrating it in several examples. An important notion following from introduction of the quantum ratio is that the elementary particles (thus the electron and the photon) are quantum mechanical, even when the environment-induced decoherence turns them into a mixed state. Decoherence and classical state should not be identified. This simple observation, further illustrationed by the consideration of a few atomic or molecular processes, may have significant implications on the way quantum mechanics works in biological systems.